Engagement of β2 integrins induces surface expression of β1 integrin receptors in human neutrophils

Abstract

Induction of β1 integrin (CD49/CD29) expression in polymorphonuclear leukocytes (PMN) has been shown to be associated with transendothelial migration recently. Yet, β1 integrin expression is relatively insensitive to cell activation with soluble agonists, such as N-formyl-methionyl-leucyl-phenylalanine (fMLP). We hypothesized that β2 integrins (CD11/CD18), critically involved in PMN adhesion and extravasation, may play a role in regulating β1 integrin expression in PMN. Antibody cross-linking of CD18, mimicking adhesion-dependent engagement of β2 integrins, resulted in rapid, tyrosine kinase-dependent upregulation of β1 integrins. This response was potentiated by simultaneous chemoattractant (fMLP) stimulation of PMN. Moreover, upregulation of β1 integrins evoked by CD18 cross-linking was found to support adhesion of fMLP-stimulated PMN to matrix proteins and also was critical for the ability of PMN to migrate in collagen gels in response to a gradient of fMLP. Taken together, these data demonstrate that engagement of β2 integrins in human PMN induces β1 integrin expression in these cells of significance for their migration in the extravascular tissue. Thus, β2 integrins may serve the function to regulate PMN locomotion in extravascular tissue via receptor crosstalk with β1 integrins.