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F Wojnarowska - One of the best experts on this subject based on the ideXlab platform.

  • Basement Membrane Zone and dermal extracellular matrix of the vulva vagina and amnion an immunohistochemical study with comparison with non reproductive epithelium
    Australasian Journal of Dermatology, 2010
    Co-Authors: Chingchi Chi, A Prenter, S Cooper, Shuhui Wang, F Wojnarowska
    Abstract:

    Background/Objectives:  The Basement Membrane Zone (BMZ) is an anatomically defined region present in all types of skin and mucosa, linking the epithelium to the mesenchyme with a complex structure to provide adhesion. Altered antigenic expression of the BMZ is implicated in interface dermatoses, and the BMZ is targeted by autoantibodies in subepidermal immunobullous dermatoses. This study aims to compare the antigenic expression of the BMZ and the dermal extracellular matrix in female genital skin and mucosa and amnion, with non-reproductive skin and mucosa. Methods:  An indirect immunofluorescence technique was used to compare the antigenic expression of hemidesmosome, lamina lucida, anchoring filaments, lamina densa, anchoring fibrils and extracellular matrix in samples of non-reproductive skin (three), oral mucosa (three), vulval skin (two), vagina (three) and amnion (four). Results:  Antigenic expression was similar in the stratified epithelium of reproductive and non-reproductive skin and mucosa, but differed in the simple cuboidal epithelium of amnion, which had reduced expression of dermal-associated antigens. Conclusions:  The BMZ and dermal extracellular matrix of vagina and vulva are very similar to those of non-reproductive skin and mucosa despite their various functions, but differs from amnion. Their antigenic expression does not fully account for the anatomical distribution of immunobullous and interface dermatoses.

  • childhood vulval lichen sclerosus autoimmunity to the Basement Membrane Zone protein bp180 and its relationship to autoimmunity
    Clinical and Experimental Dermatology, 2010
    Co-Authors: M Baldo, B Bhogal, Richard Groves, J Powell, F Wojnarowska
    Abstract:

    Lichen sclerosus (LS) is associated with autoimmune disease in female children and adults. In adult women, there are antibody and T-cell responses to proteins in the Basement Membrane Zone (BMZ). The aim of this study was to investigate reactivity to the BMZ in girls with LS. Nine girls with vulval LS were studied clinically and serologically. The presence of circulating BMZ autoantibodies was investigated. Autoimmunity was assessed by personal and family history of autoimmune diseases and autoantibodies. We detected circulating BMZ antibodies in four of the nine children, all with IgG responses. Three patients were positive by indirect immunofluorescence, one had a positive ELISA reaction to bullous pemphigoid antigen (BP)180, and three had a positive reaction on BP180 immunoblots. There was no association with autoimmune disease or clinical features. To our knowledge, this is the first study to find BMZ autoantibodies in children with vulval LS. The autoantibodies were directed at BP180 and were exclusively of the IgG class.

  • the Basement Membrane Zone of the nail
    British Journal of Dermatology, 2006
    Co-Authors: Rodney Sinclair, F Wojnarowska, I M Leigh, R.p.r. Dawber
    Abstract:

    The anatomy of the epidermis, dermis and subcutaneous tissues of the nail apparatus is distinct from that of non-appendageal skin. Apart from the demonstration of the longitudinal configuration of the dermal-epidermal junction of the nail bed, there have been no studies of the composition of the Basement Membrane Zone of the nail apparatus. We obtained three human accessory digits, including one thumb, all of which had been amputated for cosmetic reasons, and were without known pathology. Specimens were stained with a battery of monoclonal and polyclonal antibodies which target normal Basement Membrane Zone antigens, and studied by indirect immunofluorescence. This study demonstrated that the four distinct regions of the nail, namely the proximal nail fold, the nail matrix, the nail bed and the hyponychium expressed all the target antigens found in the normal non-appendageal Basement Membrane. In particular, there was normal expression of the epidermal-associated antigens, the 220- and 180-kDa bullous pemphigoid antigens, and the alpha 6 beta 4 integrin. There was also normal expression of the lamina lucida antigens LH39, GB3 and laminin. It is of interest that the dermal-associated components, namely the 285-kDa linear IgA antigen, the extracellular matrix glycoproteins chondroitin sulphate, type VII collagen and its closely associated proteins, and the poorly characterized antigen for LH24 and LH39 were all normally expressed. Fibronectin, which is not a normal Basement Membrane Zone component, was diffusely expressed in the extracellular matrix, but did not accentuate the Basement Membrane Zone.(ABSTRACT TRUNCATED AT 250 WORDS)

  • erosive lichen planus of the vulva weak circulating Basement Membrane Zone antibodies are present
    Clinical and Experimental Dermatology, 2005
    Co-Authors: S Cooper, D Dean, J Allen, Gudula Kirtschig, F Wojnarowska
    Abstract:

    The objective of this study was to investigate whether circulating Basement Membrane Zone (BMZ) antibodies are present in erosive lichen planus (LP) of the vulva. In total, 56 consecutive women with biopsy-confirmed erosive LP of the vulva were recruited from a vulval clinic in a district general hospital and teaching hospital in Oxfordshire. Indirect immunofluorescence (IgG and IgA) was performed on 56 sera, and 15 were tested to IgG subclasses (1-4). Immunoblotting was carried out on salt-split and urea-extracted epidermal skin extracts on 11. The main outcome measure was the presence or absence of staining at the BMZ. Of the 56 sera, 34 (61%) had weak (neat or 1 : 5) epidermal-binding BMZ antibodies (25 had IgG, 5 had IgA, 4 had both IgG and IgA). All 15 sera tested to IgG showed epidermal binding to one or more IgG subclasses: IgG1 (7 sera), IgG2 (7), IgG3 (7) and IgG4 (0). Immunoblotting identified IgG antibodies to bullous pemphigoid (BP)180 (10/11) and BP230 (2/11). The majority (61%) of patients with vulval erosive LP had circulating serum IgG BMZ antibodies, chiefly reacting with BP180. There was subclass restriction of the IgG response to IgG1, 2 and 3. The significance of these antibodies is uncertain, but they may be a marker for the disease.

  • the Basement Membrane Zone in patients with systemic lupus erythematosus immunofluorescence studies in the skin kidney and amniochorion
    Lupus, 2004
    Co-Authors: A M Alahlafi, P Wordsworth, L Lakasing, D Davies, F Wojnarowska
    Abstract:

    Histological studies suggest that the Basement Membrane Zone (BMZ) is the main target of tissue pathology in cutaneous lupus erythematosus (LE). The BMZ is characteristically thickened and is the s...

Razzaque A Ahmed - One of the best experts on this subject based on the ideXlab platform.

  • profile of autoantibody to Basement Membrane Zone proteins in patients with mucous Membrane pemphigoid long term follow up and influence of therapy
    Clinical Immunology, 2004
    Co-Authors: Shih Wei Yeh, Razzaque A Ahmed, Adnan Q Usman
    Abstract:

    Mucous Membrane pemphigoid (MMP) is an autoimmune mucocutaneous blistering disease characterized by autoantibodies to components within the Basement Membrane Zone. In this study, we report the titers of autoantibodies to antigens in the BMZ, in the sera of 13 patients, treated with intravenous immunoglobulin as monotherapy over a consecutive 18-month period. Using bovine gingiva lysate as substrate in an immunoblot assay, autoantibodies to human bullous pemphigoid antigens (BPAg1 and BPAg2), human beta4 integrin, and laminin 5 were measured. A statistically significant (P < 0.05) decline in the autoantibody titers to beta4-integrin was observed after 3.42 months of initiating the IVIg therapy. These titers were undetectable after 13 months of therapy. The titers of antibodies to BPAg1 and BPAg2 did not correlate with disease activity or response to therapy. Antibodies to laminins were not detected. In patients with MMP, autoantibody titers to beta4-integrin correlate with disease activity and response to therapy.

  • profile of autoantibody to Basement Membrane Zone proteins in patients with mucous Membrane pemphigoid long term follow up and influence of therapy
    Clinical Immunology, 2004
    Co-Authors: Shih Wei Yeh, Razzaque A Ahmed, Adnan Q Usman
    Abstract:

    Mucous Membrane pemphigoid (MMP) is an autoimmune mucocutaneous blistering disease characterized by autoantibodies to components within the Basement Membrane Zone. In this study, we report the titers of autoantibodies to antigens in the BMZ, in the sera of 13 patients, treated with intravenous immunoglobulin as monotherapy over a consecutive 18-month period. Using bovine gingiva lysate as substrate in an immunoblot assay, autoantibodies to human bullous pemphigoid antigens (BPAg1 and BPAg2), human β4 integrin, and laminin 5 were measured. A statistically significant (P < 0.05) decline in the autoantibody titers to β4-integrin was observed after 3.42 months of initiating the IVIg therapy. These titers were undetectable after 13 months of therapy. The titers of antibodies to BPAg1 and BPAg2 did not correlate with disease activity or response to therapy. Antibodies to laminins were not detected. In patients with MMP, autoantibody titers to β4-integrin correlate with disease activity and response to therapy.

  • bullous pemphigoid interaction of interleukin 5 anti Basement Membrane Zone antibodies and eosinophils a preliminary observation
    Cytokine, 2001
    Co-Authors: Kailash C Bhol, Suman Kumari, Razzaque A Ahmed
    Abstract:

    Bullous pemphigoid (BP) is an autoimmune blistering skin disease characterized by the presence of autoantibodies to normal components of the hemidesmosome (BPAg1 and BPAg2). Histology of skin lesions demonstrate a subepidermal vesicle and a predominantly eosinophilic dermal cellular infiltrate. Interleukin 5 (IL-5) plays a major role in eosinophil recruitment and function. Using an ELISA, we investigated the levels of IL-5 in the sera and blister fluid of BP patients with active disease and those in prolonged clinical remission treated with intravenous immunoglobulin, and compared it to that in normal controls. Significantly increased levels of IL-5 were detected in the serum and particularly the blister fluid of patients with active disease (P=0.0043) when compared to levels in normal controls. There was no significant difference in IL-5 levels in patients in prolonged clinical remission compared to normal control serum. In an immunoblot assay, using bovine gingival lysate as substrate, we determined the presence of IgG and IgE autoantibodies specific to Basement Membrane Zone proteins in blister fluid and serum of BP patients. IgG autoantibodies to BPAg1 and BPAg2 were detected in both blister fluid and serum of patients, whereas IgE autoantibodies, in much lower titers, were detected to only BPAg1. Elevated levels of blood and tissue eosinophilia were observed in these patients. Based on these data, we present a preliminary hypothesis for the initiation, progression and localization of blister formation in BP.

J Allen - One of the best experts on this subject based on the ideXlab platform.

  • erosive lichen planus of the vulva weak circulating Basement Membrane Zone antibodies are present
    Clinical and Experimental Dermatology, 2005
    Co-Authors: S Cooper, D Dean, J Allen, Gudula Kirtschig, F Wojnarowska
    Abstract:

    The objective of this study was to investigate whether circulating Basement Membrane Zone (BMZ) antibodies are present in erosive lichen planus (LP) of the vulva. In total, 56 consecutive women with biopsy-confirmed erosive LP of the vulva were recruited from a vulval clinic in a district general hospital and teaching hospital in Oxfordshire. Indirect immunofluorescence (IgG and IgA) was performed on 56 sera, and 15 were tested to IgG subclasses (1-4). Immunoblotting was carried out on salt-split and urea-extracted epidermal skin extracts on 11. The main outcome measure was the presence or absence of staining at the BMZ. Of the 56 sera, 34 (61%) had weak (neat or 1 : 5) epidermal-binding BMZ antibodies (25 had IgG, 5 had IgA, 4 had both IgG and IgA). All 15 sera tested to IgG showed epidermal binding to one or more IgG subclasses: IgG1 (7 sera), IgG2 (7), IgG3 (7) and IgG4 (0). Immunoblotting identified IgG antibodies to bullous pemphigoid (BP)180 (10/11) and BP230 (2/11). The majority (61%) of patients with vulval erosive LP had circulating serum IgG BMZ antibodies, chiefly reacting with BP180. There was subclass restriction of the IgG response to IgG1, 2 and 3. The significance of these antibodies is uncertain, but they may be a marker for the disease.

  • the Basement Membrane Zone and dermal extracellular matrix in erosive lichen planus of the vulva an immunohistochemical study demonstrating altered expression of hemidesmosome components and anchoring fibrils
    Clinical and Experimental Dermatology, 2005
    Co-Authors: S Cooper, A Prenter, D Dean, J Allen, Fenella Wojnarowska
    Abstract:

    Summary Histopathology demonstrates disruption of the basal layer of the epidermis in lichen planus (LP) and altered expression of Basement Membrane Zone (BMZ) components occurs in cutaneous and oral LP. This is the first study in erosive LP of the vulva to investigate the expression of components of the BMZ and extracellular matrix by indirect immunofluorescence. Six biopsies from lesional vulval erosive LP were compared with two biopsies from normal vulva and five biopsies from normal skin. In erosive vulval LP there was widespread disruption of several BMZ components compared to normal skin. The hemidesmosome antigens were disrupted and attenuated, or absent. Expression of lamina lucida proteins and anchoring filaments also showed some alteration. Lamina densa components were altered and in particular there was very marked thickening, streaking and fragmentation of the anchoring fibrils. Some dermal extracellular matrix proteins were increased. This study has demonstrated widespread damage to the BMZ in erosive LP of the vulva, in particular the hemidesmosomes (α6β4 integrin, BP230, BP180) and anchoring fibrils (collagen VII). This suggests an alteration in antigenic expression in the BMZ that may lead to exposure of epitopes and thus make these proteins vulnerable to attack by autoantibodies.

  • the Basement Membrane Zone and dermal extracellular matrix in erosive lichen planus of the vulva an immunohistochemical study demonstrating altered expression of hemidesmosome components and anchoring fibrils
    Clinical and Experimental Dermatology, 2005
    Co-Authors: S Cooper, A Prenter, D Dean, J Allen, Fenella Wojnarowska
    Abstract:

    Histopathology demonstrates disruption of the basal layer of the epidermis in lichen planus (LP) and altered expression of Basement Membrane Zone (BMZ) components occurs in cutaneous and oral LP. This is the first study in erosive LP of the vulva to investigate the expression of components of the BMZ and extracellular matrix by indirect immunofluorescence. Six biopsies from lesional vulval erosive LP were compared with two biopsies from normal vulva and five biopsies from normal skin. In erosive vulval LP there was widespread disruption of several BMZ components compared to normal skin. The hemidesmosome antigens were disrupted and attenuated, or absent. Expression of lamina lucida proteins and anchoring filaments also showed some alteration. Lamina densa components were altered and in particular there was very marked thickening, streaking and fragmentation of the anchoring fibrils. Some dermal extracellular matrix proteins were increased. This study has demonstrated widespread damage to the BMZ in erosive LP of the vulva, in particular the hemidesmosomes (alpha6beta4 integrin, BP230, BP180) and anchoring fibrils (collagen VII). This suggests an alteration in antigenic expression in the BMZ that may lead to exposure of epitopes and thus make these proteins vulnerable to attack by autoantibodies.

  • alterations in the Basement Membrane Zone in pili annulati hair follicles as demonstrated by electron microscopy and immunohistochemistry
    British Journal of Dermatology, 2004
    Co-Authors: Kathrin A Giehl, D Dean, J Allen, Y. H. Chuang, R.p.r. Dawber, David J P Ferguson, D De Berker, Antonella Tosti, F Wojnarowska
    Abstract:

    Summary Background  Pili annulati is a rare autosomal dominant inherited hair shaft abnormality in which clinical examination reveals alternating light and dark bands leading to a shiny appearance of the hair. The clinically light bands are the abnormal areas due to cavities within the cortex. The pathogenesis remains unknown. Objectives  To investigate the expression of the Basement Membrane Zone (BMZ) components in pili annulati hair follicles of the scalp. Methods  Transmission electron microscopy (TEM) was carried out on scalp sections of six individuals with pili annulati and six controls. Longitudinal sections of scalp tissues from four individuals with pili annulati and six normal controls were studied by immunohistochemistry with a panel of monoclonal antibodies to the following BMZ components: α6β4 integrin, laminin 5, LH39 antigen, laminin 1, collagen IV and collagen VII. Results  Using TEM, pili annulati scalp specimens exhibited a reduplicated lamina densa in the region of the root bulb in comparison with the single thin electron-dense band in controls. Using immunohistochemistry, there was a wavy BMZ in pili annulati follicles with antibodies to components of the lamina lucida, lamina densa and anchoring fibrils, whereas the BMZ in control hair follicles was as a smooth linear band. The expression of the hemidesmosome-associated α6β4 integrin was linear in both pili annulati and control hair follicles. Conclusions  Our results suggest that the genetic defect may be a mutation in proteins involved in signalling and regulation of formation and degradation of the lamina densa and sublamina densa region resulting in abnormal assembly or remodelling of the BMZ.

  • Comparison between the expression of Basement Membrane Zone antigens of human interfollicular epidermis and anagen hair follicle using indirect immunofluorescence
    The British journal of dermatology, 2003
    Co-Authors: Y. H. Chuang, D Dean, J Allen, R.p.r. Dawber, Fenella Wojnarowska
    Abstract:

    Summary Background The composition of the Basement Membrane Zone (BMZ) or dermal–epidermal junction in the interfollicular skin has been well documented. However, little is known about the BMZ or connective tissue–epithelial junction along the hair follicle. Objectives  To determine whether the BMZ antigens in the interfollicular epidermis are also present in the BMZ of the anagen hair follicle and to compare whether the expression and distribution of the BMZ components vary between the interfollicular epidermis and the anagen follicle and within different regions of the hair follicle. Methods  Longitudinal cryostat sections of scalp margin specimens from four adult patients undergoing cosmetic surgery, and without known pathology were stained with a panel of monoclonal and polyclonal antibodies to different BMZ constituents using standard indirect immunofluorescence. Results  All the BMZ antigens found in the normal interfollicular epidermis were expressed in the anagen follicle; however, there were regional variations in the intensity and patterns of fluorescence. All the antigens were expressed in a continuous linear pattern along the BMZ of the interfollicular skin, the infundibulum, and the middle part of the hair follicle. Differences were observed in the lower follicle and the hair bulb. There was continuous expression throughout the BMZ of the follicle of laminin-1 and collagen IV, but in contrast, expression of other antigens decreased down the lower follicle. There was weak or even negative staining with antibodies to α6β4 integrin, laminin-5, anchoring filaments, and type VII collagen in the outer aspect of the bulb compared with the hair papilla. In addition, there were special patterns observed along the bilateral middle and lower follicle. Conclusions  Despite the common embryological origin between the interfollicular epidermis and the hair follicle, there is variation in the expression of the BMZ antigens. This may be explained by the histological specialization and functional requirements that reflect the dynamic hair growth cycle.

Michael J Evans - One of the best experts on this subject based on the ideXlab platform.

  • reduction of collagen vii anchoring fibrils in the airway Basement Membrane Zone of infant rhesus monkeys exposed to house dust mite
    American Journal of Physiology-lung Cellular and Molecular Physiology, 2010
    Co-Authors: Michael J Evans, Michelle V Fanucchi, Lisa A Miller, Melinda Carlson, Susan J Nishio, Dallas M Hyde
    Abstract:

    Collagen VII anchoring fibrils in the Basement Membrane Zone (BMZ) are part of a supracellular anchoring network that attaches the epithelium to the BMZ. Sloughing of airway epithelium in asthmatics (creola bodies) is a pathology associated with the supracellular anchoring network. In a rhesus monkey model of house dust mite (HDM)-induced allergic asthma, we found increased deposition of collagen I in the BMZ. In this study, we determine whether HDM also affected deposition of collagen VII in the BMZ. In the developing airway of rhesus monkeys, the width of collagen VII anchoring fibrils in the BMZ was 0.02 ± 0.04 μm at 1 mo of age. At 6 mo the width had increased to 1.28 ± 0.34 μm and at 12 mo 2.15 ± 0.13 μm. In animals treated with HDM, we found a 42.2% reduction in the width of collagen VII layer in the BMZ at 6 mo (0.74 ± 0.15 μm; P < 0.05). During recovery, the rate of collagen VII deposition returned to normal. However, the amount of collagen VII lost was not recovered after 6 mo. We concluded that normal development of the collagen VII attachment between the epithelium and BMZ occurs in coordination with development of the BMZ. However, in HDM-treated animals, the collagen VII attachment with the epithelium was significantly reduced. Such a reduction in collagen VII may weaken the supracellular anchoring network and be associated with sloughing of the epithelium and formation of creola bodies in asthmatics.

  • the remodelled tracheal Basement Membrane Zone of infant rhesus monkeys after 6 months of recovery
    Clinical & Experimental Allergy, 2004
    Co-Authors: Michael J Evans, Michelle V Fanucchi, Lisa A Miller, Susan J Nishio, Gregory L Baker, L S Van Winkle, Lorraine M Pantle, Edward S Schelegle, Laurel J Gershwin, D M Hyde
    Abstract:

    Summary Background In previous studies, we showed that repeated exposure to (1) house dust mite allergen (HDMA) (Dermatophagoides farinae) caused thickening of the Basement Membrane Zone (BMZ) and (2) HDMA+oZone (O3) caused depletion of BMZ perlecan and atypical development of BMZ collagen (irregular thin areas<2.0 μm in width). Objective The purpose of this study was to determine if these remodelling changes were reversible after 6 months of recovery. Methods Rhesus monkeys were exposed to a regimen of HDMA and or O3 or filtered air (FA) for 6 months. After the exposure protocol was completed FA and O3 groups were allowed to recover in FA for 6 months. The HDMA and HDMA+O3 exposure groups recovered in a modified environment. They were re-exposed to HDMA aerosol for 2 h at monthly intervals during recovery in order to maintain sensitization for pulmonary function testing. To detect structural changes in the BMZ, collagen I and perlecan immunoreactivity were measured and compared to data from the previous papers. Results The remodelled HDMA group had a significantly thicker BMZ and after 6 months of recovery the width had not regressed. In the remodelled BMZ of the HDMA+O3 group, perlecan had returned to the BMZ after 6 months of the recovery protocol, and the thin, irregular, collagen BMZ had been resolved. Conclusion In summary, this study has shown that: (1) The width of the remodelled HDMA BMZ did not regress during a recovery protocol that included a sensitizing dose of HDMA. (2) The atypical collagen BMZ in the HDMA+O3 BMZ was resolved in the absence of O3. (3) Depletion of perlecan from the BMZ by O3 was reversed by recovery in the absence of O3.

  • development of the pulmonary Basement Membrane Zone
    The Lung#R##N#Development Aging and the Environment, 2004
    Co-Authors: Michael J Evans, Philip L Sannes
    Abstract:

    Publisher Summary This chapter discusses the structure, composition, and the development of the pulmonary Basement Membrane Zone (BMZ). The (BMZ) is a mat-like sheet of specialized extracellular matrix (ECM) that serves as a complex interface between epithelia, peripheral nerves or muscle cells, and their surrounding tissue microenvironments. The Basement Membrane appears as three-component layers: the lamina lucida, the lamina densa and the lamina reticularis and together they make up the basal lamina. The development of the BMZ involves continuous growth of the lamina densa as the tissue grows. The type IV collagen and laminin are believed to spontaneously polymerize into networks that are joined together by entactin/nidogen. Proteoglycans are then added to this structure. This is an ongoing process and the cells involved are the adjacent epithelial or smooth muscle cells and the fibroblast layer on the other side of the BMZ. The lamina reticularis is formed postnatally, probably by the same cell types as the lamina densa, however, in contrast to the lamina densa, it does not stay at the same width, but increases in width.

  • atypical development of the tracheal Basement Membrane Zone of infant rhesus monkeys exposed to oZone and allergen
    American Journal of Physiology-lung Cellular and Molecular Physiology, 2003
    Co-Authors: Michael J Evans, Michelle V Fanucchi, Lisa A Miller, Susan J Nishio, Laura S Van Winkle, Gregory L Baker, Lorraine M Pantle, Edward S Schelegle, Laurel J Gershwin, Dallas M Hyde
    Abstract:

    Development of the Basement Membrane Zone (BMZ) occurs postnatally in the rhesus monkey. The purpose of this study was to determine whether house dust mite allergen (HDMA) plus oZone altered this process. Rhesus monkeys were exposed to a regimen of HDMA and/or oZone or filtered air for 6 mo. To detect structural changes in the BMZ, we measured immunoreactivity of collagen I. To detect functional changes in the BMZ, we measured perlecan and fibroblast growth factor-2 (FGF-2). We also measured components of the FGF-2 ternary signaling complex [fibroblast growth factor receptor-1 (FGFR-1) and syndecan-4]. The width of the BMZ was irregular in the oZone groups, suggesting atypical development of the BMZ. Perlecan was also absent from the BMZ. In the absence of perlecan, FGF-2 was not bound to the BMZ. However, FGF-2 immunoreactivity was present in basal cells, the lateral intercellular space (LIS), and attenuated fibroblasts. FGFR-1 immunoreactivity was downregulated, and syndecan-4 immunoreactivity was upregulated in the basal cells. This suggests that FGF-2 in basal cells and LIS may be bound to the syndecan-4. We conclude that oZone and HDMA plus oZone effected incorporation of perlecan into the BMZ, resulting in atypical development of the BMZ. These changes are associated with specific alterations in the regulation of FGF-2, FGFR-1, and syndecan-4 in the airway epithelial-mesenchymal trophic unit, which may be associated with the developmental problems of lungs associated with exposure to oZone.

  • fibroblast growth factor 2 during postnatal development of the tracheal Basement Membrane Zone
    American Journal of Physiology-lung Cellular and Molecular Physiology, 2002
    Co-Authors: Michael J Evans, Michelle V Fanucchi, Susan J Nishio, Laura S Van Winkle, Gregory L Baker, April E Murphy
    Abstract:

    Thickening of the Basement Membrane Zone (BMZ) is a characteristic of several airway diseases; however, very little is known about how this process occurs. The purpose of this study was to define d...

Susan J Nishio - One of the best experts on this subject based on the ideXlab platform.

  • reduction of collagen vii anchoring fibrils in the airway Basement Membrane Zone of infant rhesus monkeys exposed to house dust mite
    American Journal of Physiology-lung Cellular and Molecular Physiology, 2010
    Co-Authors: Michael J Evans, Michelle V Fanucchi, Lisa A Miller, Melinda Carlson, Susan J Nishio, Dallas M Hyde
    Abstract:

    Collagen VII anchoring fibrils in the Basement Membrane Zone (BMZ) are part of a supracellular anchoring network that attaches the epithelium to the BMZ. Sloughing of airway epithelium in asthmatics (creola bodies) is a pathology associated with the supracellular anchoring network. In a rhesus monkey model of house dust mite (HDM)-induced allergic asthma, we found increased deposition of collagen I in the BMZ. In this study, we determine whether HDM also affected deposition of collagen VII in the BMZ. In the developing airway of rhesus monkeys, the width of collagen VII anchoring fibrils in the BMZ was 0.02 ± 0.04 μm at 1 mo of age. At 6 mo the width had increased to 1.28 ± 0.34 μm and at 12 mo 2.15 ± 0.13 μm. In animals treated with HDM, we found a 42.2% reduction in the width of collagen VII layer in the BMZ at 6 mo (0.74 ± 0.15 μm; P < 0.05). During recovery, the rate of collagen VII deposition returned to normal. However, the amount of collagen VII lost was not recovered after 6 mo. We concluded that normal development of the collagen VII attachment between the epithelium and BMZ occurs in coordination with development of the BMZ. However, in HDM-treated animals, the collagen VII attachment with the epithelium was significantly reduced. Such a reduction in collagen VII may weaken the supracellular anchoring network and be associated with sloughing of the epithelium and formation of creola bodies in asthmatics.

  • the remodelled tracheal Basement Membrane Zone of infant rhesus monkeys after 6 months of recovery
    Clinical & Experimental Allergy, 2004
    Co-Authors: Michael J Evans, Michelle V Fanucchi, Lisa A Miller, Susan J Nishio, Gregory L Baker, L S Van Winkle, Lorraine M Pantle, Edward S Schelegle, Laurel J Gershwin, D M Hyde
    Abstract:

    Summary Background In previous studies, we showed that repeated exposure to (1) house dust mite allergen (HDMA) (Dermatophagoides farinae) caused thickening of the Basement Membrane Zone (BMZ) and (2) HDMA+oZone (O3) caused depletion of BMZ perlecan and atypical development of BMZ collagen (irregular thin areas<2.0 μm in width). Objective The purpose of this study was to determine if these remodelling changes were reversible after 6 months of recovery. Methods Rhesus monkeys were exposed to a regimen of HDMA and or O3 or filtered air (FA) for 6 months. After the exposure protocol was completed FA and O3 groups were allowed to recover in FA for 6 months. The HDMA and HDMA+O3 exposure groups recovered in a modified environment. They were re-exposed to HDMA aerosol for 2 h at monthly intervals during recovery in order to maintain sensitization for pulmonary function testing. To detect structural changes in the BMZ, collagen I and perlecan immunoreactivity were measured and compared to data from the previous papers. Results The remodelled HDMA group had a significantly thicker BMZ and after 6 months of recovery the width had not regressed. In the remodelled BMZ of the HDMA+O3 group, perlecan had returned to the BMZ after 6 months of the recovery protocol, and the thin, irregular, collagen BMZ had been resolved. Conclusion In summary, this study has shown that: (1) The width of the remodelled HDMA BMZ did not regress during a recovery protocol that included a sensitizing dose of HDMA. (2) The atypical collagen BMZ in the HDMA+O3 BMZ was resolved in the absence of O3. (3) Depletion of perlecan from the BMZ by O3 was reversed by recovery in the absence of O3.

  • atypical development of the tracheal Basement Membrane Zone of infant rhesus monkeys exposed to oZone and allergen
    American Journal of Physiology-lung Cellular and Molecular Physiology, 2003
    Co-Authors: Michael J Evans, Michelle V Fanucchi, Lisa A Miller, Susan J Nishio, Laura S Van Winkle, Gregory L Baker, Lorraine M Pantle, Edward S Schelegle, Laurel J Gershwin, Dallas M Hyde
    Abstract:

    Development of the Basement Membrane Zone (BMZ) occurs postnatally in the rhesus monkey. The purpose of this study was to determine whether house dust mite allergen (HDMA) plus oZone altered this process. Rhesus monkeys were exposed to a regimen of HDMA and/or oZone or filtered air for 6 mo. To detect structural changes in the BMZ, we measured immunoreactivity of collagen I. To detect functional changes in the BMZ, we measured perlecan and fibroblast growth factor-2 (FGF-2). We also measured components of the FGF-2 ternary signaling complex [fibroblast growth factor receptor-1 (FGFR-1) and syndecan-4]. The width of the BMZ was irregular in the oZone groups, suggesting atypical development of the BMZ. Perlecan was also absent from the BMZ. In the absence of perlecan, FGF-2 was not bound to the BMZ. However, FGF-2 immunoreactivity was present in basal cells, the lateral intercellular space (LIS), and attenuated fibroblasts. FGFR-1 immunoreactivity was downregulated, and syndecan-4 immunoreactivity was upregulated in the basal cells. This suggests that FGF-2 in basal cells and LIS may be bound to the syndecan-4. We conclude that oZone and HDMA plus oZone effected incorporation of perlecan into the BMZ, resulting in atypical development of the BMZ. These changes are associated with specific alterations in the regulation of FGF-2, FGFR-1, and syndecan-4 in the airway epithelial-mesenchymal trophic unit, which may be associated with the developmental problems of lungs associated with exposure to oZone.

  • fibroblast growth factor 2 during postnatal development of the tracheal Basement Membrane Zone
    American Journal of Physiology-lung Cellular and Molecular Physiology, 2002
    Co-Authors: Michael J Evans, Michelle V Fanucchi, Susan J Nishio, Laura S Van Winkle, Gregory L Baker, April E Murphy
    Abstract:

    Thickening of the Basement Membrane Zone (BMZ) is a characteristic of several airway diseases; however, very little is known about how this process occurs. The purpose of this study was to define d...

  • fibroblast growth factor 2 in remodeling of the developing Basement Membrane Zone in the trachea of infant rhesus monkeys sensitized and challenged with allergen
    Laboratory Investigation, 2002
    Co-Authors: Michael J Evans, Michelle V Fanucchi, Susan J Nishio, Laura S Van Winkle, Gregory L Baker, April E Murphy, Philip L Sannes, Edward S Schelegle, Laurel J Gershwin, Charles G Plopper
    Abstract:

    Remodeling of the epithelial Basement Membrane Zone (BMZ) involves increased deposition of collagen, resulting in thickening of the BMZ. The current study focuses on fibroblast growth factor-2 (FGF-2) in the tracheal BMZ in house dust mite allergen (HDMA)-sensitized infant rhesus monkeys, challenged with HDMA at a time when the BMZ is undergoing active postnatal development. To detect structural changes in the BMZ, we measured collagens I, III, and V. To detect changes in the function of the BMZ, we measured immunoreactivity of the heparan sulfate proteoglycan, perlecan, and FGF-2. We found significant thickening of the tracheal BMZ (p < 0.05) with each of these parameters. We also found that all HDMA tracheal samples expressed thin focal areas of the BMZ associated with leukocyte trafficking. These areas were depleted of perlecan and FGF-2; however, increased FGF-2 immunoreactivity was present in the adjacent basal cells. We conclude that basal cells and FGF-2 are involved with significant remodeling of the BMZ in the developing trachea of infant rhesus monkeys exposed to HDMA.