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Am. J. Respir. Cell Mol. Biol., Volume 25, Number 6, December, 2001 685-691

Secretion of Interleukin-1 Receptor Antagonist from Human Mast Cells after Immunoglobulin E-Mediated Activation and after Segmental Antigen Challenge

David D. Hagaman, Yoshimichi Okayama, Claudio D'Ambrosio, Calman Prussin, Alasdair M. Gilfillan, and Dean D. Metcalfe

Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland

Mast cells produce substances with antiinflammatory properties in addition to their capacity to release proinflammatory mediators. To further probe the antiinflammatory aspect of mast-cell function we investigated the ability of human mast cells (huMCs) to produce interleukin (IL)-1 receptor antagonist (IL-1ra) in response to high-affinity Fc receptor for immunoglobulin E (Fcalpha RI) aggregation, and examined IL-1ra in bronchoalveolar lavage fluid (BALF) to determine whether it might be of mast-cell origin. Using a ribonuclease protection assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA), IL-1ra message and protein were found to be constitutively expressed in cultured huMCs. Upon stimulation through Fcalpha RI, IL-1ra message was upregulated in huMCs and IL-1ra protein secreted from cultured huMCs and isolated human lung mast cells. By immunoblot analysis, huMCs were found to produce the 17-kD form of IL-1ra and the presence of IL-1ra in human lung mast cells was confirmed by immunohistochemistry. In BALF obtained from allergic asthmatic subjects, IL-1ra production increased after specific antigen challenge, with the 17-kD isoform of IL-1ra predominating. These findings demonstrate that huMCs produce and release IL-1ra after Fcalpha RI aggregation, which may contribute to a local inhibition of IL-1-dependent effects on inflammation in the lung.

Abbreviations: bronchoalveolar lavage fluid, BALF; bovine serum albumin, BSA; enzyme-linked immunosorbent assay, ELISA; high-affinity Fc receptor for IgE, Fcepsilon RI; human mast cell, huMC; immunoglobulin, Ig; interleukin, IL; IL-1 receptor antagonist, IL-1ra; IL-1 receptor 1, IL-1RI; IL-1 receptor 2, IL-1RII; messenger RNA, mRNA; anti-4-hydroxy-3-nitrophenylacetyl, NP; phosphate-buffered saline, PBS; recombinant human, rh; Tris-buffered saline, TBS.




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Copyright © 2001 American Thoracic Society.