Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden
Correspondence: Joachim Werr, Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden. E-mail: joachim.werr{at}fyfa.ki.se
Induction of ß1 integrin (CD49/CD29) expression in polymorphonuclear leukocytes (PMN) has been shown to be associated with transendothelial migration recently. Yet, ß1 integrin expression is relatively insensitive to cell activation with soluble agonists, such as N-formyl-methionyl-leucyl-phenylalanine (fMLP). We hypothesized that ß2 integrins (CD11/CD18), critically involved in PMN adhesion and extravasation, may play a role in regulating ß1 integrin expression in PMN. Antibody cross-linking of CD18, mimicking adhesion-dependent engagement of ß2 integrins, resulted in rapid, tyrosine kinase-dependent upregulation of ß1 integrins. This response was potentiated by simultaneous chemoattractant (fMLP) stimulation of PMN. Moreover, upregulation of ß1 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 ß2 integrins in human PMN induces ß1 integrin expression in these cells of significance for their migration in the extravascular tissue. Thus, ß2 integrins may serve the function to regulate PMN locomotion in extravascular tissue via receptor crosstalk with ß1 integrins.
Key Words: inflammation leukocytes adhesion extravasation migration
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