Recombinant tumour necrosis factor-α and platelet-activating factor synergistically increase intercellular adhesion molecule-1 and E-selectin-dependent neutrophil adherence to endothelium in vitro

A. Sterner-Kock, R. K. Braun, M. D. Schrenzel, D. M. Hyde

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Abstract

Neutrophil adhesion to microvascular endothelium at sites of acute inflammation is regulated by both chemotactic peptides and lipid-derived mediators. Tumour necrosis factor-α (TNF-α) is a pro-inflammatory peptide that up-regulates endothelial expression of intercellular adhesion molecule-1 (ICAM-1) and endothelial leucocyte adhesion molecule-1 (E-selectin), while platelet-activating factor (PAF) is a potent lipid mediator that induces vascular changes via an unknown mechanism. Both have been shown to increase leucocyte-endothelial adhesion in various in vitro models of acute inflammation; however, the combined effects of recombinant TNF-α (rTNF-α) and PAF on neutrophil endothelium adhesion have not been well described. In this study, we found rTNF-α at 0.5ng/ml and PAF at 10μM acted synergistically to increase neutrophil adherence to cultured umbilical vein endothelial cells 4hr after stimulation. This increased neutrophil-endothelial adhesion was, in part, dependent on up-regulated expression of ICAM-1 and E-selectin since application of anti-ICAM1 and anti-E-selectin F(ab′)2 fragments markedly diminished adhesion. Cultures stimulated with rTNF-α (0.5ng/ml) or PAF (10μM) alone did not show a significant increase in neutrophil adhesion, and neither ICAM-1 nor E-selectin expression was up-regulated as determined by flow cytometric analysis of endothelial cells. These results indicate that rTNF-α and PAF act synergistically to increase neutrophil-endothelial adhesion by stimulating endothelial expression of ICAM-1 and E-selectin and, thus, may play important roles in the onset and severity of acute inflammatory reactions.

Original languageEnglish (US)
Pages (from-to)454-460
Number of pages7
JournalImmunology
Volume87
Issue number3
StatePublished - 1996

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ASJC Scopus subject areas

  • Immunology

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