Interleukin-1 induces interleukin-8 secretion from endothelial cells by a juxtacrine mechanism

Gilles Kaplanski, Catherine Farnarier, Solange Kaplanski, Reuven Porat, Leland Shapiro, Pierre Bongrand, Charles A. Dinarello

Research output: Contribution to journalArticlepeer-review


Inflammation is characterized by migration of neutrophils through the endothelium, and the chemokine interleukin-8 (IL-8) appears to be involved. We asked whether adherence of cells bearing a membrane-form of interleukin 1 (IL-1) induces IL-8 secretion from human umbilical vein endothelial cells (HUVEC) and fibroblasts. Human peripheral blood mononuclear cells (PBMC) were stimulated with endotoxin for 12 hours and then fixed for 4 hours with paraformaldehyde. When these cells were added to HUVEC or fibroblasts, IL-8 production was induced. This stimulation by fixed PBMC was attributed to IL- 1, because pretreatment of HUVEC or fibroblasts with IL-1 receptor antagonist (IL-1Ra) reduced the induction by 95% and 80%, respectively, P < .005. Using anti-IL-1α monoclonal antibodies, reduction was complete, whereas anti-lL- 1β had no effect. IL-1α was shown on the surface of monocytes by fluorescence-activated cell sorter (FACS) analysis. Blockade of IL-1 receptors on PBMC did not affect the activity of membrane-associated IL-1α, indicating that IL-1 is not anchored to the membrane through its receptors. However, PBMC treated with D-mannose before fixation resulted in a loss of activity; this loss of activity was associated with release of IL-1α, not IL-1β, into the supernatant. Thus, anchoring of IL-1α to the membrane may be via a lectin or mannose receptor-like interaction. Blockade of membrane IL-1α required a 30-fold and fivefold excess of IL-1Ra compared with the amount required to block soluble IL-1β and IL-1α, respectively. We conclude that the fixed PBMC IL-8 inducing activity is almost entirely caused by IL- 1, that this represents IL-1α bound to a surface lectin or mannose receptor on the monocyte, and that it functions in inflammation via juxtacrine interactions.

Original languageEnglish
Pages (from-to)4242-4248
Number of pages7
Issue number12
StatePublished - 15 Dec 1994


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