Cultured human vascular endothelial cells acquire adhesiveness for neutrophils after stimulation with interleukin 1, endotoxin, and tumor-promoting phorbol diesters

R. P. Schleimer, B. K. Rutledge

Research output: Contribution to journalArticle

236 Scopus citations

Abstract

Cultured human vascular endothelial cells obtained from umbilical cord veins were observed to acquire adhesive properties for purified neutrophils after exposure to IL 1, endotoxin, and tumor-promoting phorbol diesters. Adhesiveness induced by IL 1 and endotoxin had similar kinetics of onset, producing no change after 30 min incubation and reaching optimal change by 4 hr of incubation. The phorbol diester TPA induced changes in adhesiveness more rapidly, with half maximal increase induced by a 15- to 30-min exposure. TPA, but not IL 1 or LPS, induced significant morphologic changes in the endothelial cell monolayer. None of the stimuli decreased endothelial cell viability. All stimuli induced increased adhesiveness at relevant concentrations, i.e., endotoxin, 0.01 to 1 μg/ml; IL 1, 0.5 to 2 U/ml; and TPA, 1 to 30 ng/ml. Structure activity relationships among phorbol diesters indicate that the response occurs through a typical phorbol diester 'receptor'. A protein synthesis inhibitor (cycloheximide) and an RNA synthesis inhibitor (actinomycin D) prevented the acquisition of adhesiveness stimulated by IL 1 and endotoxin but not by TPA. In addition, TPA showed a differential temperature sensitivity in inducing adhesiveness in endothelial cells. IL 1 and endotoxin did not produce the effect with a 4-hr incubation at 22° or 4°C, whereas TPA was effective at these lower temperatures. Purified human IL 2 and recombinant-derived interferon-γ failed to induce adhesiveness in vascular endothelial cells, indicating that this is not a general property of lymphokines. We conclude that endothelium may, under some circumstances, play an active role in producing a leukocyte infiltrate at a local tissue site by acquiring adhesive properties. The production of IL 1 by tissue macrophages, etc., may serve as an important initiator of an inflammatory cell infiltrate. Finally, an action of tumor-promoting phorbol diesters in increasing endothelial cell adhesiveness, combined with their known effects in activating leukocytes, may help explain the extraordinary inflammatory potency of these compounds.

Original languageEnglish (US)
Pages (from-to)649-654
Number of pages6
JournalJournal of Immunology
Volume136
Issue number2
StatePublished - 1986

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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