Neutrophil stimulation by recombinant cytokines and a factor produced by IL-1-treated human synovial cell cultures.
Neutrophil accumulation and activation are early events in the inflammatory response in vivo. Using human recombinant forms of the putative inflammatory mediators interleukin-1 (IL-1) and tumour necrosis factor (TNF alpha) we were unable to detect direct effects on human neutrophil locomotion or intracellular free calcium concentration ([Ca2+]i) in vitro. Human recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) was able to stimulate significant locomotion, but was unable to elevate neutrophil [Ca2+]i. In contrast, supernatant from cultured human synovial cells that had been treated with human recombinant IL-1 alpha (28 pM) released a factor that stimulated both neutrophil locomotion and elevated neutrophil [Ca2+]i. Our studies demonstrate that the production of this factor is time-dependent, requiring exposure of the synovial cells to IL-1 for more than 4 hr, is not influenced by cyclo-oxygenase or lipo-oxygenase inhibition, but can be abolished by dexamethasone (100 nM) or actinomycin D (0.8 microM). The factor has a molecular weight above 10,000 and does not cross-react with anti-C5a antisera. IL-1 beta and TNF alpha were also able to stimulate its production. Our findings suggest that the neutrophil accumulation that is known to occur in response to IL-1 in vivo may be a consequence of the local production of such a factor.
Watson
M L
ML
Department of Pharmacology, Hunterian Institute, Royal College of Surgeons, London, U.K.
Lewis
G P
GP
Westwick
J
J
D001685:Biological Factors / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D002465:Cell Movement; D002478:Cells, Cultured; D016207:Cytokines; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D013583:Synovial Membrane / Q000276:immunology*; D014462:Ultrafiltration
D001685:Biological Factors; D016207:Cytokines; D007375:Interleukin-1; D002118:Calcium