Engagement of beta2 integrins induces surface expression of beta1 integrin receptors in human neutrophils.
Induction of beta1 integrin (CD49/CD29) expression in polymorphonuclear leukocytes (PMN) has been shown to be associated with transendothelial migration recently. Yet, beta1 integrin expression is relatively insensitive to cell activation with soluble agonists, such as N-formyl-methionyl-leucyl-phenylalanine (fMLP). We hypothesized that beta2 integrins (CD11/CD18), critically involved in PMN adhesion and extravasation, may play a role in regulating 1 integrin expression in PMN. Antibody cross-linking of CD18, mimicking adhesion-dependent engagement of beta2 integrins, resulted in rapid, tyrosine kinase-dependent upregulation of beta1 integrins. This response was potentiated by simultaneous chemoattractant (fMLP) stimulation of PMN. Moreover, upregulation of beta1 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 beta2 integrins in human PMN induces beta1 integrin expression in these cells of significance for their migration in the extravascular tissue. Thus, beta2 integrins may serve the function to regulate PMN locomotion in extravascular tissue via receptor crosstalk with beta1 integrins.
Werr
J
J
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. joachim.werr@fyfa.ki.se
Eriksson
E E
EE
Hedqvist
P
P
Lindbom
L
L
D001692:Biological Transport; D018845:CD11 Antigens / Q000502:physiology*; D018821:CD18 Antigens / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002630:Chemotactic Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology; D003094:Collagen; D005353:Fibronectins; D005782:Gels; D006801:Humans; D019012:Integrin beta1 / Q000096:biosynthesis* / Q000235:genetics; D018613:Microscopy, Confocal; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D009195:Peroxidase / Q000032:analysis; D015854:Up-Regulation / Q000187:drug effects
D018845:CD11 Antigens; D018821:CD18 Antigens; D002630:Chemotactic Factors; D005353:Fibronectins; D005782:Gels; D019012:Integrin beta1; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003094:Collagen; D009195:Peroxidase