The Experts below are selected from a list of 3528 Experts worldwide ranked by ideXlab platform
Mark R. Ackermann - One of the best experts on this subject based on the ideXlab platform.
-
Human respiratory syncytial virus A2 strain replicates and induces innate immune responses by respiratory epithelia of neonatal lambs.
International journal of experimental pathology, 2009Co-Authors: Alicia K. Olivier, Jack M. Gallup, Marcia M.m.a. De Macedo, Steven M. Varga, Mark R. AckermannAbstract:Human respiratory syncytial virus (hRSV) is a pneumovirus that causes significant respiratory disease in premature and full-term infants. It was our hypothesis that a common strain of RSV, strain A2, would infect, cause pulmonary pathology, and alter respiratory epithelial innate immune responses in neonatal lambs similarly to RSV infection in human neonates. Newborn lambs between 2 and 3 days of age were inoculated intrabronchially with RSV strain A2. The lambs were sacrificed at days 3, 6, and 14 days postinoculation. Pulmonary lesions in the 6-day postinoculation group were typical of RSV infection including bronchiolitis with neutrophils and mild peribronchiolar interstitial pneumonia. RSV mRNA and antigen were detected by qPCR and immunohistochemistry, respectively with peak mRNA levels and antigen at day 6. Expression of surfactant proteins A and D, sheep Beta-Defensin-1 and thyroid transcription factor-1 mRNA were also assessed by real-time qPCR. There was a significant increase in surfactant A and D mRNA expression in RSV-infected animals at day 6 postinoculation. There were no significant changes in sheep Beta-Defensin-1 and thyroid transcription factor-1 mRNA expression. This study shows that neonatal lambs can be infected with RSV strain A2 and the pulmonary pathology mimics that of RSV infection in human infants thereby making the neonatal lamb a useful animal model to study disease pathogenesis and therapeutics. RSV infection induces increased expression of surfactant proteins A and D in lambs, which may also be an important feature of infection in newborn infants.
-
Expression of select immune genes (surfactant proteins A and D, sheep Beta Defensin 1, and toll-like receptor 4) by respiratory epithelia is developmentally regulated in the preterm neonatal lamb.
Developmental and comparative immunology, 2006Co-Authors: David K. Meyerholz, Kenji Kawashima, Jack M. Gallup, Branka Grubor, Mark R. AckermannAbstract:Preterm infants experience enhanced susceptibility and severity to respiratory syncytial virus (RSV) infection. Terminal airway epithelium is an important site of RSV infection and the extent of local innate immune gene expression is poorly understood. In this study, expression of surfactant proteins A and D (SP-AD), sheep Beta Defensin 1 (SBD1), and toll-like receptor 4 (TLR4) mRNA were determined in whole lung homogenates from lambs. SP-AD and TLR4 mRNA expression increased (p
-
expression of select immune genes surfactant proteins a and d sheep Beta Defensin 1 and toll like receptor 4 by respiratory epithelia is developmentally regulated in the preterm neonatal lamb
Developmental and Comparative Immunology, 2006Co-Authors: David K. Meyerholz, Kenji Kawashima, Jack M. Gallup, Branka Grubor, Mark R. AckermannAbstract:Preterm infants experience enhanced susceptibility and severity to respiratory syncytial virus (RSV) infection. Terminal airway epithelium is an important site of RSV infection and the extent of local innate immune gene expression is poorly understood. In this study, expression of surfactant proteins A and D (SP-AD), sheep Beta Defensin 1 (SBD1), and toll-like receptor 4 (TLR4) mRNA were determined in whole lung homogenates from lambs. SP-AD and TLR4 mRNA expression increased (p<0.05) from late gestation to term birth. In addition, gene expression of LCM-retrieved type II pneumocytes (CD208+), adjacent epithelium (CD208−) and bronchial epithelium demonstrated that bronchiole-alveolar junction epithelium (combined CD208+/−) had significant (p<0.05) developmental increases in SP-AD, SBD1 and TLR4 mRNA, whereas CD208+ cells had statistically significant increases only with SP-A mRNA. Using immunofluorescence, SP-AD antigen distribution and intensity were also greater with developmental age. These studies show reduced SBD1, SP-AD, and TLR4 expression in the preterm lung and this may underlie enhanced RSV susceptibility.
-
Differential expression of sheep Beta-Defensin-1 and -2 and interleukin 8 during acute Mannheimia haemolytica pneumonia.
Microbial pathogenesis, 2004Co-Authors: Mark R. Ackermann, David K. Meyerholz, Jack M. Gallup, Branka Grubor, Joseph Zabner, Richard B. Evans, Charles W. Brockus, Kim A. BrogdenAbstract:Abstract Beta-Defensins are antimicrobial peptides produced by several cell types, including respiratory epithelia and leukocytes. Expression of some Beta-Defensins is increased by bacterial-induced inflammatory responses whereas expression of other Beta-Defensins is constitutive. Two Beta-Defensins are expressed in lungs of sheep (sheep Beta-Defensin-1 and -2; SBD-1/-2) and expression of SBD-1 is increased during parainfluenza virus type 3 (PI-3) infection. The effect of Mannheimia haemolytica , a Gram-negative bacteria known to induce expression of bovine Beta-Defensins and NF-kappa B in lung, has not been determined for SBD-1/-2. In this study, different concentrations of M. haemolytica were inoculated into pulmonary bronchi of lambs. SBD-1 and SBD-2 mRNA levels detected by real time reverse transcriptase polymerase chain reaction in lung homogenates did not increase. In fact, SBD-1 mRNA levels were significantly decreased with the highest administered inoculum concentration (10 9 ). In contrast, mRNA levels of interleukin-8 (IL-8) were significantly increased over controls and progressively increased with M. haemolytica concentrations. Co-inoculation of M. haemolytica with xylitol, an osmotic agent, did not alter mRNA levels of SBD-1, SBD-2 or IL-8. SBD-1 mRNA expression was detected in lung epithelia, but not in leukocytes. This study suggests that SDB-1 expression occurs in epithelia and decreases during severe bacterial pneumonia, which is in contrast to the increase that occurs with PI-3 infection.
Sergio Crovella - One of the best experts on this subject based on the ideXlab platform.
-
DEFB1 polymorphisms and HIV-1 mother-to-child transmission in Zambian population
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine the Federation of Asia and , 2018Co-Authors: Luisa Zupin, Ludovica Segat, Vania Polesello, Anselmo Jiro Kamada, Louise Kuhn, Sergio CrovellaAbstract:Introduction: Human Beta Defensin-1 (hBD-1) is a component of the innate immune system, the first line of defence against pathogens, already reported as involved in the susceptibility to HIV-1 infe...
-
Human Beta Defensin-1 is involved in the susceptibility to adeno-tonsillar hypertrophy
International journal of pediatric otorhinolaryngology, 2018Co-Authors: Luisa Zupin, Fulvio Celsi, Martina Bresciani, Eva Orzan, Domenico Leonardo Grasso, Sergio CrovellaAbstract:Abstract Introduction Innate immunity molecules are known to play a pivotal role in the homeostasis of the oral mucosa, permitting the presence of commensal microflora and, at the same time, providing a first line of defense against pathogens attempting to invade the oral cavity. Tonsils represent the local immune tissue in oral cavity, being able to provide a non-specific response to pathogens; however, in the presence of microbes or foreign materials present in the mouth tonsils could became infected and develop chronic inflammation, thus leading to hypertrophy. The etiology of the disease is multifactorial depending upon environmental and host factors, the latter including molecules of mucosal innate immunity. Methods Ninety-five children with adeno-tonsillar hypertrophy subjected to adeno-tonsillectomy were recruited at the pediatric otorhinolaryngology service of the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste (Italy). The specimen discarded from the surgery were used for genomic DNA extraction and genotyping, for mRNA extraction and gene expression analysis, finally the samples were cut and used to prepare slides to perform immunohistochemistry. Results Functional polymorphisms within DEFB1 gene, encoding the human Beta Defensin-1 (hBD-1), were analyzed finding association between DEFB1 rare haplotypes and susceptibility to adeno-tonsillar hypertrophy. DEFB1 mRNA expression was detected in the tonsils and the hBD-1 protein was localized at the epithelia of tonsils mainly in the proximity of the basal lamina. Conclusion Our findings lead us to hypothesize an involvement of hBD-1 mediated innate immunity in the modulation of the susceptibility towards adeno-tonsillar hypertrophy development.
-
Beta Defensin-1 gene polymorphisms and susceptibility to atypical squamous cells of undetermined significance lesions in Italian gynecological patients.
Journal of medical virology, 2014Co-Authors: Giorgia Casalicchio, Sergio Crovella, Nadia Freato, Iva Maestri, Manola Comar, Ludovica SegatAbstract:The role of the human Beta-Defensin 1 (hBD-1) in the susceptibility to the onset of the Atypical Squamous Cells of Undetermined Significance (ASCUS) lesion, in the presence or not of HPV infection, is still unknown. In the current study, the three functional single nucleotide polymorphisms (SNPs) -52G > A, -44C > G, and -20G > A at the 5' un-translated region (UTR) of DEFB1 gene, encoding hBD-1, were analyzed in ASCUS lesion gynecological patients and healthy women from the north-east of Italy (Trieste). Cervical samples from 249 European-Caucasian women were collected, screened for HPV and cytologically evaluated; DEFB1 genotyping has been performed by direct sequencing. No significant differences were found for -52G > A, -44C > G, and -20G > A SNPs allele and genotype frequencies between women with and without ASCUS lesions. DEFB1 minor haplotypes were significantly more frequent in ASCUS lesion positive than negative women, associating with an increased risk of this type of lesion. When women were stratified according to HPV infection status, significant differences in the distribution of -52G > A SNP genotype frequencies were found: the presence of the A allele in the homozygous genotype A/A associated with a lower risk of developing ASCUS lesions in HPV negative women. DEFB1 minor haplotypes were also associated with an increased risk of developing ASCUS lesions, being significantly more frequent in HPV negative women with lesions, than without lesions. Although these results highlight the possible involvement of DEFB1, further studies are needed to support the role of DEFB1 in the modulation of the susceptibility to ASCUS lesions.
-
DEFB1 polymorphisms are involved in susceptibility to human papillomavirus infection in Brazilian gynaecological patients
Memorias do Instituto Oswaldo Cruz, 2014Co-Authors: Ludovica Segat, Luisa Zupin, Ronald Moura, Antonio Victor Campos Coelho, Bárbara Simas Chagas, Antonio Carlos De Freitas, Sergio CrovellaAbstract:The human Beta Defensin 1 (hBD-1) antimicrobial peptide is a member of the innate immune system known to act in the first line of defence against microorganisms, including viruses such as human papillomavirus (HPV). In this study, five functional polymorphisms (namely g-52G>A, g-44C>G and g-20G>A in the 5’UTR and c.*5G>A and c.*87A>G in the 3’UTR) in the DEFB1 gene encoding for hBD-1 were analysed to investigate the possible involvement of these genetic variants in susceptibility to HPV infection and in the development of HPV-associated lesions in a population of Brazilian women. The DEFB1 g-52G>A and c.*5G>A single-nucleotide polymorphisms (SNPs) and the GCAAA haplotype showed associations with HPV-negative status; in particular, the c.*5G>A SNP was significantly associated after multiple test corrections. These findings suggest a possible role for the constitutively expressed Beta Defensin-1 peptide as a natural defence against HPV in the genital tract mucosa.
-
Beta Defensin 1 gene defb1 polymorphisms are not associated with atopic dermatitis in children and adolescents from northeast brazil recife pernambuco
International Journal of Dermatology, 2010Co-Authors: Sergio Crovella, Ludovica Segat, Rafael Lima Guimarães, Lucas André Cavalcanti Brandão, Cíntia Renata Costa Rocha, Valentina Zanin, C Trevisiol, José Luiz De Lima FilhoAbstract:Background Atopic dermatitis (AD) is a common inflammatory skin disease resulting from the interplay between environmental, immunological and genetic factors. In our study, we investigated the role of three single nucleotide polymorphisms (SNPs) at 5′-UTR of DEFB1 gene, encoding for the human Beta Defensin-1, on the susceptibility to develop AD in a group of Brazilian children and adolescents. Methods Three SNPs, −20 G/A (rs11362), −44 C/G (rs1800972), and −52 G/A (rs1799946) at 5′-UTR of DEFB1 gene were genotyped in two groups of children and adolescents, one affected by AD (96 subjects), the other healthy (191 individuals), from northeast Brazil. Results −44 C/G frequencies were comparable between the two groups. The −20 GG genotype was more frequent in AD subjects than in healthy controls; the −52 GG, conversely, was more frequent in healthy controls than in AD. However, both these differences did not reach statistical significance. Also, association between SNPs and AD severity has been shown. The analysis of DEFB1 haplotypes did not highlight any association of the three SNPs with AD development or disease severity. Conclusions Our results seem to exclude a role for the −44 C/G DEFB1 SNPs on the pathogenesis and severity of AD, while for the −20 C/G and −52 G/A, even if not statistically significant, we evidenced a slight trend for susceptibility (−20 GG) and protection (−52 GG) for the development of AD. However, as controversial findings have been reported in the literature, the role of DEFB1 in the development of AD and in the severity of the phenotype deserves further investigation.
Jack M. Gallup - One of the best experts on this subject based on the ideXlab platform.
-
Human respiratory syncytial virus A2 strain replicates and induces innate immune responses by respiratory epithelia of neonatal lambs.
International journal of experimental pathology, 2009Co-Authors: Alicia K. Olivier, Jack M. Gallup, Marcia M.m.a. De Macedo, Steven M. Varga, Mark R. AckermannAbstract:Human respiratory syncytial virus (hRSV) is a pneumovirus that causes significant respiratory disease in premature and full-term infants. It was our hypothesis that a common strain of RSV, strain A2, would infect, cause pulmonary pathology, and alter respiratory epithelial innate immune responses in neonatal lambs similarly to RSV infection in human neonates. Newborn lambs between 2 and 3 days of age were inoculated intrabronchially with RSV strain A2. The lambs were sacrificed at days 3, 6, and 14 days postinoculation. Pulmonary lesions in the 6-day postinoculation group were typical of RSV infection including bronchiolitis with neutrophils and mild peribronchiolar interstitial pneumonia. RSV mRNA and antigen were detected by qPCR and immunohistochemistry, respectively with peak mRNA levels and antigen at day 6. Expression of surfactant proteins A and D, sheep Beta-Defensin-1 and thyroid transcription factor-1 mRNA were also assessed by real-time qPCR. There was a significant increase in surfactant A and D mRNA expression in RSV-infected animals at day 6 postinoculation. There were no significant changes in sheep Beta-Defensin-1 and thyroid transcription factor-1 mRNA expression. This study shows that neonatal lambs can be infected with RSV strain A2 and the pulmonary pathology mimics that of RSV infection in human infants thereby making the neonatal lamb a useful animal model to study disease pathogenesis and therapeutics. RSV infection induces increased expression of surfactant proteins A and D in lambs, which may also be an important feature of infection in newborn infants.
-
Expression of select immune genes (surfactant proteins A and D, sheep Beta Defensin 1, and toll-like receptor 4) by respiratory epithelia is developmentally regulated in the preterm neonatal lamb.
Developmental and comparative immunology, 2006Co-Authors: David K. Meyerholz, Kenji Kawashima, Jack M. Gallup, Branka Grubor, Mark R. AckermannAbstract:Preterm infants experience enhanced susceptibility and severity to respiratory syncytial virus (RSV) infection. Terminal airway epithelium is an important site of RSV infection and the extent of local innate immune gene expression is poorly understood. In this study, expression of surfactant proteins A and D (SP-AD), sheep Beta Defensin 1 (SBD1), and toll-like receptor 4 (TLR4) mRNA were determined in whole lung homogenates from lambs. SP-AD and TLR4 mRNA expression increased (p
-
expression of select immune genes surfactant proteins a and d sheep Beta Defensin 1 and toll like receptor 4 by respiratory epithelia is developmentally regulated in the preterm neonatal lamb
Developmental and Comparative Immunology, 2006Co-Authors: David K. Meyerholz, Kenji Kawashima, Jack M. Gallup, Branka Grubor, Mark R. AckermannAbstract:Preterm infants experience enhanced susceptibility and severity to respiratory syncytial virus (RSV) infection. Terminal airway epithelium is an important site of RSV infection and the extent of local innate immune gene expression is poorly understood. In this study, expression of surfactant proteins A and D (SP-AD), sheep Beta Defensin 1 (SBD1), and toll-like receptor 4 (TLR4) mRNA were determined in whole lung homogenates from lambs. SP-AD and TLR4 mRNA expression increased (p<0.05) from late gestation to term birth. In addition, gene expression of LCM-retrieved type II pneumocytes (CD208+), adjacent epithelium (CD208−) and bronchial epithelium demonstrated that bronchiole-alveolar junction epithelium (combined CD208+/−) had significant (p<0.05) developmental increases in SP-AD, SBD1 and TLR4 mRNA, whereas CD208+ cells had statistically significant increases only with SP-A mRNA. Using immunofluorescence, SP-AD antigen distribution and intensity were also greater with developmental age. These studies show reduced SBD1, SP-AD, and TLR4 expression in the preterm lung and this may underlie enhanced RSV susceptibility.
-
Differential expression of sheep Beta-Defensin-1 and -2 and interleukin 8 during acute Mannheimia haemolytica pneumonia.
Microbial pathogenesis, 2004Co-Authors: Mark R. Ackermann, David K. Meyerholz, Jack M. Gallup, Branka Grubor, Joseph Zabner, Richard B. Evans, Charles W. Brockus, Kim A. BrogdenAbstract:Abstract Beta-Defensins are antimicrobial peptides produced by several cell types, including respiratory epithelia and leukocytes. Expression of some Beta-Defensins is increased by bacterial-induced inflammatory responses whereas expression of other Beta-Defensins is constitutive. Two Beta-Defensins are expressed in lungs of sheep (sheep Beta-Defensin-1 and -2; SBD-1/-2) and expression of SBD-1 is increased during parainfluenza virus type 3 (PI-3) infection. The effect of Mannheimia haemolytica , a Gram-negative bacteria known to induce expression of bovine Beta-Defensins and NF-kappa B in lung, has not been determined for SBD-1/-2. In this study, different concentrations of M. haemolytica were inoculated into pulmonary bronchi of lambs. SBD-1 and SBD-2 mRNA levels detected by real time reverse transcriptase polymerase chain reaction in lung homogenates did not increase. In fact, SBD-1 mRNA levels were significantly decreased with the highest administered inoculum concentration (10 9 ). In contrast, mRNA levels of interleukin-8 (IL-8) were significantly increased over controls and progressively increased with M. haemolytica concentrations. Co-inoculation of M. haemolytica with xylitol, an osmotic agent, did not alter mRNA levels of SBD-1, SBD-2 or IL-8. SBD-1 mRNA expression was detected in lung epithelia, but not in leukocytes. This study suggests that SDB-1 expression occurs in epithelia and decreases during severe bacterial pneumonia, which is in contrast to the increase that occurs with PI-3 infection.
David K. Meyerholz - One of the best experts on this subject based on the ideXlab platform.
-
Expression of select immune genes (surfactant proteins A and D, sheep Beta Defensin 1, and toll-like receptor 4) by respiratory epithelia is developmentally regulated in the preterm neonatal lamb.
Developmental and comparative immunology, 2006Co-Authors: David K. Meyerholz, Kenji Kawashima, Jack M. Gallup, Branka Grubor, Mark R. AckermannAbstract:Preterm infants experience enhanced susceptibility and severity to respiratory syncytial virus (RSV) infection. Terminal airway epithelium is an important site of RSV infection and the extent of local innate immune gene expression is poorly understood. In this study, expression of surfactant proteins A and D (SP-AD), sheep Beta Defensin 1 (SBD1), and toll-like receptor 4 (TLR4) mRNA were determined in whole lung homogenates from lambs. SP-AD and TLR4 mRNA expression increased (p
-
expression of select immune genes surfactant proteins a and d sheep Beta Defensin 1 and toll like receptor 4 by respiratory epithelia is developmentally regulated in the preterm neonatal lamb
Developmental and Comparative Immunology, 2006Co-Authors: David K. Meyerholz, Kenji Kawashima, Jack M. Gallup, Branka Grubor, Mark R. AckermannAbstract:Preterm infants experience enhanced susceptibility and severity to respiratory syncytial virus (RSV) infection. Terminal airway epithelium is an important site of RSV infection and the extent of local innate immune gene expression is poorly understood. In this study, expression of surfactant proteins A and D (SP-AD), sheep Beta Defensin 1 (SBD1), and toll-like receptor 4 (TLR4) mRNA were determined in whole lung homogenates from lambs. SP-AD and TLR4 mRNA expression increased (p<0.05) from late gestation to term birth. In addition, gene expression of LCM-retrieved type II pneumocytes (CD208+), adjacent epithelium (CD208−) and bronchial epithelium demonstrated that bronchiole-alveolar junction epithelium (combined CD208+/−) had significant (p<0.05) developmental increases in SP-AD, SBD1 and TLR4 mRNA, whereas CD208+ cells had statistically significant increases only with SP-A mRNA. Using immunofluorescence, SP-AD antigen distribution and intensity were also greater with developmental age. These studies show reduced SBD1, SP-AD, and TLR4 expression in the preterm lung and this may underlie enhanced RSV susceptibility.
-
Differential expression of sheep Beta-Defensin-1 and -2 and interleukin 8 during acute Mannheimia haemolytica pneumonia.
Microbial pathogenesis, 2004Co-Authors: Mark R. Ackermann, David K. Meyerholz, Jack M. Gallup, Branka Grubor, Joseph Zabner, Richard B. Evans, Charles W. Brockus, Kim A. BrogdenAbstract:Abstract Beta-Defensins are antimicrobial peptides produced by several cell types, including respiratory epithelia and leukocytes. Expression of some Beta-Defensins is increased by bacterial-induced inflammatory responses whereas expression of other Beta-Defensins is constitutive. Two Beta-Defensins are expressed in lungs of sheep (sheep Beta-Defensin-1 and -2; SBD-1/-2) and expression of SBD-1 is increased during parainfluenza virus type 3 (PI-3) infection. The effect of Mannheimia haemolytica , a Gram-negative bacteria known to induce expression of bovine Beta-Defensins and NF-kappa B in lung, has not been determined for SBD-1/-2. In this study, different concentrations of M. haemolytica were inoculated into pulmonary bronchi of lambs. SBD-1 and SBD-2 mRNA levels detected by real time reverse transcriptase polymerase chain reaction in lung homogenates did not increase. In fact, SBD-1 mRNA levels were significantly decreased with the highest administered inoculum concentration (10 9 ). In contrast, mRNA levels of interleukin-8 (IL-8) were significantly increased over controls and progressively increased with M. haemolytica concentrations. Co-inoculation of M. haemolytica with xylitol, an osmotic agent, did not alter mRNA levels of SBD-1, SBD-2 or IL-8. SBD-1 mRNA expression was detected in lung epithelia, but not in leukocytes. This study suggests that SDB-1 expression occurs in epithelia and decreases during severe bacterial pneumonia, which is in contrast to the increase that occurs with PI-3 infection.
Branka Grubor - One of the best experts on this subject based on the ideXlab platform.
-
Expression of select immune genes (surfactant proteins A and D, sheep Beta Defensin 1, and toll-like receptor 4) by respiratory epithelia is developmentally regulated in the preterm neonatal lamb.
Developmental and comparative immunology, 2006Co-Authors: David K. Meyerholz, Kenji Kawashima, Jack M. Gallup, Branka Grubor, Mark R. AckermannAbstract:Preterm infants experience enhanced susceptibility and severity to respiratory syncytial virus (RSV) infection. Terminal airway epithelium is an important site of RSV infection and the extent of local innate immune gene expression is poorly understood. In this study, expression of surfactant proteins A and D (SP-AD), sheep Beta Defensin 1 (SBD1), and toll-like receptor 4 (TLR4) mRNA were determined in whole lung homogenates from lambs. SP-AD and TLR4 mRNA expression increased (p
-
expression of select immune genes surfactant proteins a and d sheep Beta Defensin 1 and toll like receptor 4 by respiratory epithelia is developmentally regulated in the preterm neonatal lamb
Developmental and Comparative Immunology, 2006Co-Authors: David K. Meyerholz, Kenji Kawashima, Jack M. Gallup, Branka Grubor, Mark R. AckermannAbstract:Preterm infants experience enhanced susceptibility and severity to respiratory syncytial virus (RSV) infection. Terminal airway epithelium is an important site of RSV infection and the extent of local innate immune gene expression is poorly understood. In this study, expression of surfactant proteins A and D (SP-AD), sheep Beta Defensin 1 (SBD1), and toll-like receptor 4 (TLR4) mRNA were determined in whole lung homogenates from lambs. SP-AD and TLR4 mRNA expression increased (p<0.05) from late gestation to term birth. In addition, gene expression of LCM-retrieved type II pneumocytes (CD208+), adjacent epithelium (CD208−) and bronchial epithelium demonstrated that bronchiole-alveolar junction epithelium (combined CD208+/−) had significant (p<0.05) developmental increases in SP-AD, SBD1 and TLR4 mRNA, whereas CD208+ cells had statistically significant increases only with SP-A mRNA. Using immunofluorescence, SP-AD antigen distribution and intensity were also greater with developmental age. These studies show reduced SBD1, SP-AD, and TLR4 expression in the preterm lung and this may underlie enhanced RSV susceptibility.
-
Differential expression of sheep Beta-Defensin-1 and -2 and interleukin 8 during acute Mannheimia haemolytica pneumonia.
Microbial pathogenesis, 2004Co-Authors: Mark R. Ackermann, David K. Meyerholz, Jack M. Gallup, Branka Grubor, Joseph Zabner, Richard B. Evans, Charles W. Brockus, Kim A. BrogdenAbstract:Abstract Beta-Defensins are antimicrobial peptides produced by several cell types, including respiratory epithelia and leukocytes. Expression of some Beta-Defensins is increased by bacterial-induced inflammatory responses whereas expression of other Beta-Defensins is constitutive. Two Beta-Defensins are expressed in lungs of sheep (sheep Beta-Defensin-1 and -2; SBD-1/-2) and expression of SBD-1 is increased during parainfluenza virus type 3 (PI-3) infection. The effect of Mannheimia haemolytica , a Gram-negative bacteria known to induce expression of bovine Beta-Defensins and NF-kappa B in lung, has not been determined for SBD-1/-2. In this study, different concentrations of M. haemolytica were inoculated into pulmonary bronchi of lambs. SBD-1 and SBD-2 mRNA levels detected by real time reverse transcriptase polymerase chain reaction in lung homogenates did not increase. In fact, SBD-1 mRNA levels were significantly decreased with the highest administered inoculum concentration (10 9 ). In contrast, mRNA levels of interleukin-8 (IL-8) were significantly increased over controls and progressively increased with M. haemolytica concentrations. Co-inoculation of M. haemolytica with xylitol, an osmotic agent, did not alter mRNA levels of SBD-1, SBD-2 or IL-8. SBD-1 mRNA expression was detected in lung epithelia, but not in leukocytes. This study suggests that SDB-1 expression occurs in epithelia and decreases during severe bacterial pneumonia, which is in contrast to the increase that occurs with PI-3 infection.