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F M Cunningham - One of the best experts on this subject based on the ideXlab platform.
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protein kinase c pkc isotype profile in eosinophils from ponies with Sweet Itch and role in histamine induced eosinophil activation
Veterinary Immunology and Immunopathology, 2003Co-Authors: E C Greenaway, F M Cunningham, M F Sepulveda, Nigel T GoodeAbstract:Abstract Eosinophils have been implicated in the pathogenesis of the seasonal equine allergic skin disease, Sweet Itch. Protein kinase C (PKC) is involved in regulating eosinophil function and antigen challenge has been reported to alter PKC isotype expression in blood eosinophils from allergic human subjects. Here we have compared the pattern of PKC isotype expression in eosinophils from Sweet Itch ponies with that in cells from normal ponies both during the active and inactive phases of the disease. A role for PKC in histamine-induced eosinophil activation was also investigated. Conventional PKCs α and β, novel PKCs δ and e and atypical PKCs ι and ζ were identified in eosinophils pooled from four allergic ponies during the inactive phase, when no clinical signs were evident. The PKC isotypes, like those in eosinophils from normal ponies, were located primarily in the particulate fraction of the cell. Isotype expression in cells from normal and allergic animals did not appear to be different. In contrast, during the active phase of the disease, when the Sweet Itch ponies had clinical signs, the expression of PKCs β, e and ι in eosinophils from these animals appeared to be increased relative to that in cells from normal ponies. When PKC expression in eosinophils from five individual normal and Sweet Itch ponies was compared, small, but statistically significant, increases in PKCe and PKCδ expression were evident in eosinophils from the Sweet Itch ponies during the active and inactive phases, respectively. The non-selective PKC inhibitors, staurosporine and Ro31-8220, significantly reduced histamine-induced superoxide production. Use of Go6976, an inhibitor of conventional PKCs, suggested that PKCα and/or β were involved and that there was significantly greater inhibition of the response in eosinophils obtained from Sweet Itch ponies during the active phase. There was no significant difference in histamine-induced superoxide production by eosinophils from allergic and normal ponies and the functional significance of the increased PKC isotype expression in eosinophils from Sweet Itch ponies relative to that in cells from healthy animals remains to be established.
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Protein kinase C (PKC) isotype profile in eosinophils from ponies with Sweet Itch and role in histamine-induced eosinophil activation.
Veterinary immunology and immunopathology, 2003Co-Authors: E C Greenaway, F M Cunningham, M F Sepulveda, Nigel T GoodeAbstract:Eosinophils have been implicated in the pathogenesis of the seasonal equine allergic skin disease, Sweet Itch. Protein kinase C (PKC) is involved in regulating eosinophil function and antigen challenge has been reported to alter PKC isotype expression in blood eosinophils from allergic human subjects. Here we have compared the pattern of PKC isotype expression in eosinophils from Sweet Itch ponies with that in cells from normal ponies both during the active and inactive phases of the disease. A role for PKC in histamine-induced eosinophil activation was also investigated. Conventional PKCs alpha and beta, novel PKCs delta and epsilon and atypical PKCs iota and zeta were identified in eosinophils pooled from four allergic ponies during the inactive phase, when no clinical signs were evident. The PKC isotypes, like those in eosinophils from normal ponies, were located primarily in the particulate fraction of the cell. Isotype expression in cells from normal and allergic animals did not appear to be different. In contrast, during the active phase of the disease, when the Sweet Itch ponies had clinical signs, the expression of PKCs beta, epsilon and iota in eosinophils from these animals appeared to be increased relative to that in cells from normal ponies. When PKC expression in eosinophils from five individual normal and Sweet Itch ponies was compared, small, but statistically significant, increases in PKC epsilon and PKCdelta expression were evident in eosinophils from the Sweet Itch ponies during the active and inactive phases, respectively. The non-selective PKC inhibitors, staurosporine and Ro31-8220, significantly reduced histamine-induced superoxide production. Use of Gö6976, an inhibitor of conventional PKCs, suggested that PKCalpha and/or beta were involved and that there was significantly greater inhibition of the response in eosinophils obtained from Sweet Itch ponies during the active phase. There was no significant difference in histamine-induced superoxide production by eosinophils from allergic and normal ponies and the functional significance of the increased PKC isotype expression in eosinophils from Sweet Itch ponies relative to that in cells from healthy animals remains to be established.
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Differential activation of platelets from normal and allergic ponies by PAF and ADP
Inflammation Research, 2000Co-Authors: S.r. Bailey, M.j. Andrews, J. Elliott, F M CunninghamAbstract:Objective and Design: Altered platelet responsiveness has been demonstrated in human atopic dermatitis. This study has compared the in vitro function of platelets from normal ponies and those with the allergic skin disease, Sweet Itch.¶ Subjects: Ponies with a clinical history of Sweet Itch and normal ponies were used as blood donors.¶ Methods: PAF and ADP-induced platelet aggregation was measured and TxB_2 production quantitated at the time of maximal aggregation; 12-HETE was additionally measured in some samples. Agonist-induced release of ^3[H]5-HT was also studied.¶ Results: Although both PAF and ADP caused equine platelet aggregation, only PAF stimulated eicosanoid and 5-HT release. There were no differences between the responses of platelets from allergic and normal ponies to PAF or ADP (analysis of variance).¶ Conclusions: There is no evidence of altered platelet responsiveness in ponies with Sweet Itch. The profile of responses to PAF and ADP suggest differential activation of intracellular signalling pathways in equine platelets.
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characterisation of lymphocyte subpopulations in the skin and circulation of horses with Sweet Itch culicoides hypersensitivity
Equine Veterinary Journal, 1999Co-Authors: Joanne Mckelvie, A P Foster, F M Cunningham, A S HamblinAbstract:Summary Circulating lymphocyte numbers are elevated in horses with the allergic skin disease Sweet Itch and skin lesions are typified by an infiltrate of eosinophils and mononuclear cells, the latter of which have not been fully characterised. The aim of the present study was to characterise the lymphocyte subpopulations in the circulation and skin of ponies with Sweet Itch by flow cytometry and a newly developed modified alkaline phosphatase immunohistochemical technique. Sweet Itch ponies were found to have significantly greater numbers of circulating CD5+ and CD4+ T-lymphocytes than normal animals. Increased numbers of CD3+ T-lymphocytes, most of which were CD4+, and eosinophils were present in the skin of these animals following intradermal injection of a Culicoides antigen extract (97 ± 21 vs. 449 ± 49 CD3+ T-lymphocytes/mm2 in deep dermis of vehicle vs. antigen injected sites; 83 ± 8% CD4+ T-lymphocytes at antigen injected site). T-lymphocytes, which are thought to be important in the pathogenesis of human allergic skin disease, may therefore contribute to the development of Sweet Itch lesions via the release of cytokines which can cause eosinophil accumulation and activation. An understanding of the pathology of this disease may lead to a more rational approach to therapy.
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actions of paf receptor antagonists in horses with the allergic skin disease Sweet Itch
Inflammation Research, 1995Co-Authors: A P Foster, P Lees, F M CunninghamAbstract:Platelet activating factor (PAF) mimics the effects ofCulicoides antigen by inducing oedema and inflammatory cell accumulation in the dermis of horses with the allergic skin disease, Sweet Itch. PAF could therefore contribute to antigen-induced inflammatory changes in these horses. We now report that intravenous administration of the PAF receptor antagonist WEB 2086 (3mgkg−1), at a dose that inhibited the vascular and cellular responses to PAF in Sweet Itch horses, reducedCulicoides antigen-induced oedema at 1 h by 73% and at 8h by 71% (p<0.05). Neutrophil accumulation and eosinophil recruitment were not significantly reduced by WEB 2086 or a second hetrazepine PAF receptor antagonist WEB 2170 (0.1mgkg−1). These findings suggest a key role for PAF in oedema formation, but not inflammatory cell accumulation, induced byCulicoides antigen in the skin of Sweet Itch horses.
A P Foster - One of the best experts on this subject based on the ideXlab platform.
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Culicoides antigen extract stimulates equine blood mononuclear (BMN) cell proliferation and the release of eosinophil adherence-inducing factor(s)
Research in Veterinary Science, 2001Co-Authors: J. Mckelvie, A P Foster, A S Hamblin, Fiona M. CunninghamAbstract:Abstract Intradermal injection of a Culicoides antigen extract (CAgX) induces T lymphocyte and eosinophil accumulation in the skin of horses with Sweet Itch. Blood mononuclear ( BMN ) cells from normal ponies proliferate when stimulated by mitogen (phytohaemagglutinin, PHA ) or antigen (tetanus toxoid, TT ) and, as shown here, release soluble factor(s) that induce eosinophil adherence. CAgX also caused concentration dependent proliferation of BMN cells from Sweet Itch and normal ponies [stimulation index: 29 (13) and 17 (7) for BMN cells from Sweet Itch and normal ponies, respectively during the active phase of disease; 4 μg protein ml−1CAgX; 168 h]. A heat labile factor(s) which caused eosinophil adherence was also released [Sweet Itch ponies: 6.0 (1.6) per cent adherence versus 1.3 (0.4) per cent; normal ponies: 6.6 (0.5) per cent adherence versus 0.9 (0.1) per cent for supernatants from CAgX (4 μg protein ml−1; 48 hours) stimulated versus unstimulated BMN cells, respectively]. These results suggest that soluble proteins released from T lymphocytes could affect eosinophil function in the lesional skin of Sweet Itch horses.
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characterisation of lymphocyte subpopulations in the skin and circulation of horses with Sweet Itch culicoides hypersensitivity
Equine Veterinary Journal, 1999Co-Authors: Joanne Mckelvie, A P Foster, F M Cunningham, A S HamblinAbstract:Summary Circulating lymphocyte numbers are elevated in horses with the allergic skin disease Sweet Itch and skin lesions are typified by an infiltrate of eosinophils and mononuclear cells, the latter of which have not been fully characterised. The aim of the present study was to characterise the lymphocyte subpopulations in the circulation and skin of ponies with Sweet Itch by flow cytometry and a newly developed modified alkaline phosphatase immunohistochemical technique. Sweet Itch ponies were found to have significantly greater numbers of circulating CD5+ and CD4+ T-lymphocytes than normal animals. Increased numbers of CD3+ T-lymphocytes, most of which were CD4+, and eosinophils were present in the skin of these animals following intradermal injection of a Culicoides antigen extract (97 ± 21 vs. 449 ± 49 CD3+ T-lymphocytes/mm2 in deep dermis of vehicle vs. antigen injected sites; 83 ± 8% CD4+ T-lymphocytes at antigen injected site). T-lymphocytes, which are thought to be important in the pathogenesis of human allergic skin disease, may therefore contribute to the development of Sweet Itch lesions via the release of cytokines which can cause eosinophil accumulation and activation. An understanding of the pathology of this disease may lead to a more rational approach to therapy.
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actions of paf receptor antagonists in horses with the allergic skin disease Sweet Itch
Inflammation Research, 1995Co-Authors: A P Foster, P Lees, F M CunninghamAbstract:Platelet activating factor (PAF) mimics the effects ofCulicoides antigen by inducing oedema and inflammatory cell accumulation in the dermis of horses with the allergic skin disease, Sweet Itch. PAF could therefore contribute to antigen-induced inflammatory changes in these horses. We now report that intravenous administration of the PAF receptor antagonist WEB 2086 (3mgkg−1), at a dose that inhibited the vascular and cellular responses to PAF in Sweet Itch horses, reducedCulicoides antigen-induced oedema at 1 h by 73% and at 8h by 71% (p<0.05). Neutrophil accumulation and eosinophil recruitment were not significantly reduced by WEB 2086 or a second hetrazepine PAF receptor antagonist WEB 2170 (0.1mgkg−1). These findings suggest a key role for PAF in oedema formation, but not inflammatory cell accumulation, induced byCulicoides antigen in the skin of Sweet Itch horses.
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Actions of PAF receptor antagonists in horses with the allergic skin disease Sweet Itch
Inflammation Research, 1995Co-Authors: A P Foster, P Lees, F M CunninghamAbstract:Platelet activating factor (PAF) mimics the effects of Culicoides antigen by inducing oedema and inflammatory cell accumulation in the dermis of horses with the allergic skin disease, Sweet Itch. PAF could therefore contribute to antigen-induced inflammatory changes in these horses. We now report that intravenous administration of the PAF receptor antagonist WEB 2086 (3mgkg^−1), at a dose that inhibited the vascular and cellular responses to PAF in Sweet Itch horses, reduced Culicoides antigen-induced oedema at 1 h by 73% and at 8h by 71% (p
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platelet activating factor mimics antigen induced cutaneous inflammatory responses in Sweet Itch horses
Veterinary Immunology and Immunopathology, 1995Co-Authors: A P Foster, P Lees, F M CunninghamAbstract:Abstract Hypersensitivity responses to biting flies such as Culicoides are believed to be the cause of Sweet Itch, a seasonal intensely pruritic skin condition of horses. Little is known about the mediators released by antigen in the skin of affected horses. In the present study the cutaneous vascular and cellular responses to intradermally injected platelet activating factor (PAF) have been characterised in Sweet Itch cases during the active phase of the disease and compared with those of Culicoides antigen extract. Histamine was used as a positive control in vascular permeability studies. Responses were also examined in 4 of the 5 Sweet Itch cases during the inactive phase of the disease. Normal ponies were used as controls. PAF-induced increases in vascular permeability that were dose-related (0.001–1 μg per site) and of a similar magnitude in Sweet Itch and normal animals. Antigen (0.5–50 μg per site) also caused dose-related wheal formation in Sweet Itch cases during the active, but not the inactive, phase of the disease. This effect was biphasic, with maximal responses occurring at 1 and 8 h. An increase in vascular permeability occurred in normal ponies only after administration of the highest dose of antigen tested. Interestingly, histamine (0.02 μg per site) induced wheals were significantly smaller in the affected, compared with the normal, group, both during the active and inactive phases. PAF and antigen caused neutrophil accumulation in the skin of Sweet Itch and normal animals during both the active and inactive phases of the disease. Eosinophil recruitment was also observed but only in the affected group and, in the case of PAF, during the active, but not the inactive, phase. Antigen additionally caused the accumulation of mononuclear cells in the skin of Sweet Itch cases during the active phase, PAF induced a small increase in mononuclear cell numbers in these animals but the increase was not statistically significant. These findings demonstrate that PAF mimics the effects of Culicoides antigen during the active phase of the disease. Hence, PAF, like histamine, may play a role in the pathogenesis of antigen-induced responses in the skin of Sweet Itch horses.
P Lees - One of the best experts on this subject based on the ideXlab platform.
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Actions of PAF receptor antagonists in horses with the allergic skin disease Sweet Itch
Inflammation Research, 1995Co-Authors: A P Foster, P Lees, F M CunninghamAbstract:Platelet activating factor (PAF) mimics the effects of Culicoides antigen by inducing oedema and inflammatory cell accumulation in the dermis of horses with the allergic skin disease, Sweet Itch. PAF could therefore contribute to antigen-induced inflammatory changes in these horses. We now report that intravenous administration of the PAF receptor antagonist WEB 2086 (3mgkg^−1), at a dose that inhibited the vascular and cellular responses to PAF in Sweet Itch horses, reduced Culicoides antigen-induced oedema at 1 h by 73% and at 8h by 71% (p
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actions of paf receptor antagonists in horses with the allergic skin disease Sweet Itch
Inflammation Research, 1995Co-Authors: A P Foster, P Lees, F M CunninghamAbstract:Platelet activating factor (PAF) mimics the effects ofCulicoides antigen by inducing oedema and inflammatory cell accumulation in the dermis of horses with the allergic skin disease, Sweet Itch. PAF could therefore contribute to antigen-induced inflammatory changes in these horses. We now report that intravenous administration of the PAF receptor antagonist WEB 2086 (3mgkg−1), at a dose that inhibited the vascular and cellular responses to PAF in Sweet Itch horses, reducedCulicoides antigen-induced oedema at 1 h by 73% and at 8h by 71% (p<0.05). Neutrophil accumulation and eosinophil recruitment were not significantly reduced by WEB 2086 or a second hetrazepine PAF receptor antagonist WEB 2170 (0.1mgkg−1). These findings suggest a key role for PAF in oedema formation, but not inflammatory cell accumulation, induced byCulicoides antigen in the skin of Sweet Itch horses.
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platelet activating factor mimics antigen induced cutaneous inflammatory responses in Sweet Itch horses
Veterinary Immunology and Immunopathology, 1995Co-Authors: A P Foster, P Lees, F M CunninghamAbstract:Abstract Hypersensitivity responses to biting flies such as Culicoides are believed to be the cause of Sweet Itch, a seasonal intensely pruritic skin condition of horses. Little is known about the mediators released by antigen in the skin of affected horses. In the present study the cutaneous vascular and cellular responses to intradermally injected platelet activating factor (PAF) have been characterised in Sweet Itch cases during the active phase of the disease and compared with those of Culicoides antigen extract. Histamine was used as a positive control in vascular permeability studies. Responses were also examined in 4 of the 5 Sweet Itch cases during the inactive phase of the disease. Normal ponies were used as controls. PAF-induced increases in vascular permeability that were dose-related (0.001–1 μg per site) and of a similar magnitude in Sweet Itch and normal animals. Antigen (0.5–50 μg per site) also caused dose-related wheal formation in Sweet Itch cases during the active, but not the inactive, phase of the disease. This effect was biphasic, with maximal responses occurring at 1 and 8 h. An increase in vascular permeability occurred in normal ponies only after administration of the highest dose of antigen tested. Interestingly, histamine (0.02 μg per site) induced wheals were significantly smaller in the affected, compared with the normal, group, both during the active and inactive phases. PAF and antigen caused neutrophil accumulation in the skin of Sweet Itch and normal animals during both the active and inactive phases of the disease. Eosinophil recruitment was also observed but only in the affected group and, in the case of PAF, during the active, but not the inactive, phase. Antigen additionally caused the accumulation of mononuclear cells in the skin of Sweet Itch cases during the active phase, PAF induced a small increase in mononuclear cell numbers in these animals but the increase was not statistically significant. These findings demonstrate that PAF mimics the effects of Culicoides antigen during the active phase of the disease. Hence, PAF, like histamine, may play a role in the pathogenesis of antigen-induced responses in the skin of Sweet Itch horses.
E Marti - One of the best experts on this subject based on the ideXlab platform.
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detection of igg and ige serum antibodies to culicoides salivary gland antigens in horses with insect dermal hypersensitivity Sweet Itch
Equine Veterinary Journal, 2010Co-Authors: A D Wilson, L J Harwood, Sigriður Bjornsdottir, E MartiAbstract:Summary We postulated that all horses exposed to the bites of Culcoides (midges) would have an antibody response to the antigen secreted in Culcoides saliva, but that IgE antibody would be restricted to allergic individuals. Using immunohistology on sections of fixed Culicoides, we have demonstrated the presence of antibodies in horse serum which recognise Culicoides salivary glands. Antibodies were detected in the serum of horses with insect dermal hypersensitivity and in the serum of normal horses exposed to Culicoides bites. In contrast, no antibodies were detected in serum from native Icelandic ponies which had not been exposed to Culicoides. Anti-salivary gland IgG antibodies were detected in serum from both allergic and healthy horses exposed to Culicoides. IgE antibodies were only detected in horses with signs of insect dermal hypersensitivity, they were not found in serum of healthy controls nor in the serum of horses with a history of hypersensitivity but in remission at the time of sampling. Using western blotting we confirmed the presence of antibodies to Culicoides antigens and demonstrated that individual horses react to different numbers of antigens. This paper demonstrates the ability of serum from allergic horses to detect Culcoides antigens and will enable further studies to isolate and characterise the allergens.
Nigel T Goode - One of the best experts on this subject based on the ideXlab platform.
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protein kinase c pkc isotype profile in eosinophils from ponies with Sweet Itch and role in histamine induced eosinophil activation
Veterinary Immunology and Immunopathology, 2003Co-Authors: E C Greenaway, F M Cunningham, M F Sepulveda, Nigel T GoodeAbstract:Abstract Eosinophils have been implicated in the pathogenesis of the seasonal equine allergic skin disease, Sweet Itch. Protein kinase C (PKC) is involved in regulating eosinophil function and antigen challenge has been reported to alter PKC isotype expression in blood eosinophils from allergic human subjects. Here we have compared the pattern of PKC isotype expression in eosinophils from Sweet Itch ponies with that in cells from normal ponies both during the active and inactive phases of the disease. A role for PKC in histamine-induced eosinophil activation was also investigated. Conventional PKCs α and β, novel PKCs δ and e and atypical PKCs ι and ζ were identified in eosinophils pooled from four allergic ponies during the inactive phase, when no clinical signs were evident. The PKC isotypes, like those in eosinophils from normal ponies, were located primarily in the particulate fraction of the cell. Isotype expression in cells from normal and allergic animals did not appear to be different. In contrast, during the active phase of the disease, when the Sweet Itch ponies had clinical signs, the expression of PKCs β, e and ι in eosinophils from these animals appeared to be increased relative to that in cells from normal ponies. When PKC expression in eosinophils from five individual normal and Sweet Itch ponies was compared, small, but statistically significant, increases in PKCe and PKCδ expression were evident in eosinophils from the Sweet Itch ponies during the active and inactive phases, respectively. The non-selective PKC inhibitors, staurosporine and Ro31-8220, significantly reduced histamine-induced superoxide production. Use of Go6976, an inhibitor of conventional PKCs, suggested that PKCα and/or β were involved and that there was significantly greater inhibition of the response in eosinophils obtained from Sweet Itch ponies during the active phase. There was no significant difference in histamine-induced superoxide production by eosinophils from allergic and normal ponies and the functional significance of the increased PKC isotype expression in eosinophils from Sweet Itch ponies relative to that in cells from healthy animals remains to be established.
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Protein kinase C (PKC) isotype profile in eosinophils from ponies with Sweet Itch and role in histamine-induced eosinophil activation.
Veterinary immunology and immunopathology, 2003Co-Authors: E C Greenaway, F M Cunningham, M F Sepulveda, Nigel T GoodeAbstract:Eosinophils have been implicated in the pathogenesis of the seasonal equine allergic skin disease, Sweet Itch. Protein kinase C (PKC) is involved in regulating eosinophil function and antigen challenge has been reported to alter PKC isotype expression in blood eosinophils from allergic human subjects. Here we have compared the pattern of PKC isotype expression in eosinophils from Sweet Itch ponies with that in cells from normal ponies both during the active and inactive phases of the disease. A role for PKC in histamine-induced eosinophil activation was also investigated. Conventional PKCs alpha and beta, novel PKCs delta and epsilon and atypical PKCs iota and zeta were identified in eosinophils pooled from four allergic ponies during the inactive phase, when no clinical signs were evident. The PKC isotypes, like those in eosinophils from normal ponies, were located primarily in the particulate fraction of the cell. Isotype expression in cells from normal and allergic animals did not appear to be different. In contrast, during the active phase of the disease, when the Sweet Itch ponies had clinical signs, the expression of PKCs beta, epsilon and iota in eosinophils from these animals appeared to be increased relative to that in cells from normal ponies. When PKC expression in eosinophils from five individual normal and Sweet Itch ponies was compared, small, but statistically significant, increases in PKC epsilon and PKCdelta expression were evident in eosinophils from the Sweet Itch ponies during the active and inactive phases, respectively. The non-selective PKC inhibitors, staurosporine and Ro31-8220, significantly reduced histamine-induced superoxide production. Use of Gö6976, an inhibitor of conventional PKCs, suggested that PKCalpha and/or beta were involved and that there was significantly greater inhibition of the response in eosinophils obtained from Sweet Itch ponies during the active phase. There was no significant difference in histamine-induced superoxide production by eosinophils from allergic and normal ponies and the functional significance of the increased PKC isotype expression in eosinophils from Sweet Itch ponies relative to that in cells from healthy animals remains to be established.
