BETA 2 integrin signaling in leukocytes.

Division of Experimental Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, Entrance 78, SE-20 502 Malmö, Sweden.

Frontiers in bioscience : a journal and virtual library 2000 Apr 1

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Members of the beta 2 integrin family are the dominating integrins expressed on leukocytes, and they play a major role in leukocyte cell-cell and cell-matrix adhesions during inflammation and other immune responses. Beta 2 integrins are signaling receptors, but they are also targets of and are functionally affected by intracellular signals. Accordingly, researchers usually discuss two types of signaling by beta 2 integrins (and integrins in general): transmission of signals into the cell following binding of ligands or counter-receptors to the integrins (outside-in signaling), and regulation of the avidity and conformation of integrins by signals generated by other receptors within the cell (inside-out signaling). In this review, our aim is to summarize what is known about the capacity of beta 2 integrins to generate outside-in signaling in leukocytes, in particular polymorphonuclear neutrophils. Results in the literature clearly demonstrate that one of the earliest events in beta 2 integrin signaling is activation of non-receptor tyrosine kinases, which in turn triggers downstream activation of various signaling pathways that affect different functional responses of the cell. We also discuss molecules of potential importance in beta 2 integrin signaling.