title: Secretion of interleukin-1 receptor antagonist from human mast cells after immunoglobulin E-mediated activation and after segmental antigen challenge.
abstract: 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.
authors.affiliation: Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1881, USA.
authors.forename: D D
authors.initials: DD
authors.lastname: Hagaman
authors.forename: Y
authors.initials: Y
authors.lastname: Okayama
authors.forename: C
authors.initials: C
authors.lastname: D'Ambrosio
authors.forename: C
authors.initials: C
authors.lastname: Prussin
authors.forename: A M
authors.initials: AM
authors.lastname: Gilfillan
authors.forename: D D
authors.initials: DD
authors.lastname: Metcalfe
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D001249:Asthma / Q000276:immunology / Q000378:metabolism; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid; D001999:Bronchoscopy; D002478:Cells, Cultured / Q000187:drug effects / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000378:metabolism; D007073:Immunoglobulin E / Q000276:immunology*; D007152:Immunologic Capping; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D008168:Lung / Q000166:cytology* / Q000276:immunology / Q000473:pathology; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D017455:Receptors, IgE / Q000276:immunology*; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D012636:Secretory Rate; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000485:Allergens; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger; D017455:Receptors, IgE; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D007073:Immunoglobulin E