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Title: | A Recombinant Fragment of Human Surfactant Protein D Suppresses Basophil Activation, Th2 and B Cell Responses in Grass Pollen-induced Allergic Inflammation |
Authors: | Singh, I Pathan, AA Layhadi, JA Parkin, R Alexandra, F Durham, SR Kishore, U Shamji, MH |
Keywords: | Allergy;Innate immunity;Recombinant fragment of human Surfactant protein D;Allergic rhinitis;T cells;Facilitated Allergen Presentation;IgE synthesis |
Issue Date: | 27-Jan-2017 |
Publisher: | American Thoracic Society |
Citation: | Qaseem AS, Singh I, Pathan AA, Layhadi JA, Parkin R, Alexandra F, Durham SR, Kishore U, Shamji MH. A Recombinant Fragment of Human Surfactant Protein D Suppresses Basophil Activation, Th2 and B Cell Responses in Grass Pollen-induced Allergic Inflammation. |
Abstract: | Rationale: rfhSP-D has been shown to suppress house dust mite and Aspergillus 74 fumigatus-induced allergic inflammation in murine models. 75 Objectives: We sought to elucidate the effect of rfhSP-D on FcεRI and CD23- 76 mediated grass pollen induced allergic inflammatory responses. 77 Methods: rfhSP-D, containing homotrimeric neck and lectin domains, was 78 expressed in Escherichia coli BL21 (λDE3) pLysS. PBMCs and sera were obtained 79 from grass pollen allergic individuals (n=27). The effect of rfhSP-D on basophil 80 activation and histamine release was measured by flow cytometry. IgE-facilitated 81 allergen binding and presentation was assessed by flow cytometry. Th2 cytokines 82 were measured in cell culture supernatants. The effect of rfhSP-D on IgE production 83 by B cells when stimulated with CD40L, IL-4 and IL-21 was also determined. 84 Results: rfhSP-D bound to Phleum pratense in a dose- and calcium-dependent 85 manner. Allergen-induced basophil responsiveness and histamine release was 86 inhibited in the presence of rfhSP-D, as measured by CD63, CD203c 87 (P=0.0086,P=0.04205), and intracellular-labelled DAO (P=0.0003,P=0.0148). The 88 binding of allergen-IgE complexes to B cells was reduced by 51%(P=0.002) in the 89 presence of rfhSP-D. This decrease was concomitant with reduction in CD23 90 expression on B cells (P<0.001). rfhSP-D suppressed allergen-driven CD27- 91 CD4+CRTH2+ T cell proliferation (P<0.01), IL-4 and IL-5 levels (all, P<0.01). 92 Moreover, rfhSP-D inhibited CD40L/IL-4 and IL-21-mediated IgE production(77.12%; 93 P=0.02) by B cells. 94 Conclusion: For the first time, we show that rfhSP-D inhibited allergen-induced 95 basophil responses at a single cell, level and suppressed CD23-mediated facilitated 5 allergen presentation and Th2 cytokine production. 96 In addition, rfhSP-D inhibited IgE 97 synthesis by B cells, which is also a novel observation. |
URI: | http://bura.brunel.ac.uk/handle/2438/15427 |
DOI: | http://dx.doi.org/10.1164/rccm.201701-0225OC |
ISSN: | 1073-449X 1535-4970 |
Appears in Collections: | Dept of Health Sciences Research Papers |
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