Ligand binding to monocyte α5β1 integrin activates the α2β1 receptor via the α5 subunit cytoplasmic domain and protein kinase C1

R. Pacifici, J. Roman, R. Kimble, R. Civitelli, C. M. Brownfield, C. Bizzarri

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Regulation of the functional status of integrin receptors plays a critical role in inflammation and tissue remodeling, as it affects cell adherence and cytokine secretion. We have previously shown that in monocytes the binding of collagen to the α2β1 integrin induces the release of IL-1, an event that is potentiated by binding of fibronectin (Fn) to the α5β1 integrin. In this study, we have investigated the mechanisms leading to this phenomenon. Fn binding to α5β1 induced intracellular signals which increased the α2β1-dependent adhesiveness of monocytes to collagen without modifications of α2β1 expression. By using Abs against the intracellular region of the α5 subunit of the α5β1 receptor, and specific inhibitors of protein kinase C (PKC), we found that the potentiation effect of Fn on monocyte IL-1 production and their adherence to collagen was dependent on an intact α5 subunit cytoplasmic domain, and required PKC activation. Although the α2β1 could be activated by several intracellular second messengers, including protein kinase A and intracellular calcium, the potentiating effect of Fn was mediated only by PKC. These data provide an example of a novel regulatory mechanism: potentiation of β1 integrin-mediated events as a result of ligand binding to another integrin of the same class. They also show that the intracellular region of α5β1 plays a critical role in transducing signals generated by ligand binding to α5β1.

Original languageEnglish
Pages (from-to)2222-2233
Number of pages12
JournalJournal of Immunology
Volume153
Issue number5
StatePublished - Jan 1 1994

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