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Postreceptor events associated with human neutrophil activation by interleukin‐8
Author(s) -
Smith Robert J.,
Sam Laurel M.,
Leach Karen L.,
Justen James M.
Publication year - 1992
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.52.1.17
Subject(s) - exocytosis , recombinant dna , biology , degranulation , microbiology and biotechnology , biochemistry , receptor , membrane , gene
Recombinant human monocyte–derived interleukin‐8 (IL‐8M), recombinant human endotheliumderived IL‐8 (IL‐8E), and a recombinant human truncated form of IL‐8 (IL‐8T) stimulated a time‐dependent ( t 1/2 ~ 2–3 s) and concentration‐dependent (0.1–100 nM) release of azurophil (myeloperoxidase) and specific (vitamin B 12 binding protein, gelatinase) granule constituents from cytochalasin B–treated human neutrophils (HNs) wherein IL‐8T = IL‐8M > IL‐8E. An increase in the cytosolic free calcium concentration ([Ca 2+ ] i ) was greater in IL‐8T– than in IL‐8M– or IL‐8E–activated HNs, and IL‐8T was more potent than either IL‐8M or IL‐8E in sequentially desensitizing the HNs to the effects of the other IL‐8 forms. IL‐8 induced a time‐ and concentration‐dependent (0.1–100 nM) increase in the production of inositol 1,4,5‐trisphosphate (IP 3 ) in HNs. U‐73122 (1‐[6‐[[17β‐3‐methoxyestra‐1,3,5(10)‐trien‐17‐yl]amino]hexyl]‐1 H ‐pyrrole‐2,5‐dione), a potent inhibitor of phospholipase C–catalyzed events in HNs, suppressed IL‐8–triggered IP 3 production, increased [Ca 2+ ] i and granule exocytosis in HNs. The membrane‐associated activity of the α and β subtypes of protein kinase C was significantly enhanced in IL‐8–activated cells.