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National Institute of Environmental Health Sciences

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Publication Detail

Title: TNF-alpha-induced transendothelial neutrophil migration is IL-8 dependent.

Authors: Smart, S J; Casale, T B

Published In Am J Physiol, (1994 Mar)

Abstract: The early phases of airway inflammation include complex interactions between leukocytes, vascular endothelium, and inflammatory cytokines. Therefore, we examined tumor necrosis factor-alpha (TNF-alpha)-induced neutrophil migration through polycarbonate filters and human umbilical vein endothelial (HUVE) cells cultured as monolayers on these filters. TNF-alpha induced both dose- and time-dependent migration of neutrophils across both barriers. At 10(-11)-10(-9) M TNF-alpha, neutrophil migration across HUVE monolayers was more than twofold greater than that observed across naked filters. Modified checkerboard experiments indicated that neutrophils crossed naked filters as a chemokinetic rather than chemotactic response. Supernatants of TNF-alpha (10(-9) M)-stimulated HUVE monolayers induced threefold greater migration of neutrophils across naked filters than 10(-9) M TNF-alpha itself, suggesting release of soluble chemotactic factor(s). Pretreatment of HUVE monolayers with actinomycin D inhibited both TNF-alpha-induced production of soluble chemotactic factors and transendothelial neutrophil migration by > 90%. Supernatants from TNF-alpha-treated HUVE cells contained significant concentrations of interleukin 8 (IL-8), and coincubation of these supernatants with anti-IL-8 decreased supernatant-induced chemotaxis. Finally, coincubation of TNF-alpha with anti-IL-8 during transmigration experiments nearly completely inhibited the increase in neutrophil migration measured across HUVE monolayers. In contrast, WEB 2086, a platelet-activating factor receptor antagonist, had no effect. Therefore, endothelial cells greatly facilitate TNF-alpha-induced transcellular migration of neutrophils. This facilitation is dependent on TNF-alpha-stimulated production of IL-8. These data further support the active role of vascular endothelium in recruiting leukocytes to sites of inflammation.

PubMed ID: 8166294 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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