Functional association of platelet endothelial cell adhesion molecule-1 and phosphoinositide 3-kinase in human neutrophils

Fabio Pellegatta, Sergio L. Chierchia, Maria Raffaella Zocchi

Research output: Contribution to journalArticlepeer-review

Abstract

In this paper we show that the engagement of the platelet-endothelial cell adhesion molecule-1 (PECAM-1/CD31) up-regulates the adhesion of human neutrophils to the EA.hy926 endothelial cell line through a phosphoinositide 3-kinase (PI3K)-dependent pathway. Indeed, LY294002 and wortmannin prevented the effect of PECAM-1/CD31 cross-linking on cell adhesion, at concentrations known to inhibit PI3K without affecting other kinases. Both compounds blocked neutrophil binding to murine fibroblasts transfected with human ICAM-1, to purified ICAM-1 protein, or to fibronectin, suggesting that PECAM-1/CD31- mediated up-regulation of β2 and β1 integrin-mediated adhesion is PI3K- sensitive. We also provide evidence for the association of PECAM-1/CD31 to PI3K, because PI3K was detectable in neutrophil lysates after PECAM-1/CD31 cross-linking and immunoprecipitation. PECAM-1/CD31-dependent recruitment of PI3K was suggested by the finding that the serine/threonine kinase p70 S6 kinase (S6K), a signaling protein downstream of PI3K, is activated in neutrophils upon PECAM-1/CD31 cross-linking, based on the appearance of serine phosphorylation in S6K immnnoprecipitates. In turn, S6K is not directly involved in the up-regulation of integrin function because rapamycin, which can inhibit S6K independent of PI3K, did not block PECAM- 1/CD31-induced adhesion of neutrophils to β1 and β2 integrin substrates. In conclusion, PECAM-1/CD31 appears to be one of the molecules functionally coupled to PI3K, suggesting that this enzyme may represent a common pathway of integrin and adhesiveness regulation in leukocytes.

Original languageEnglish
Pages (from-to)27768-27771
Number of pages4
JournalJournal of Biological Chemistry
Volume273
Issue number43
DOIs
Publication statusPublished - Oct 23 1998

ASJC Scopus subject areas

  • Biochemistry

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