Integrin alpha(2)beta(1) (VLA-2) is a principal receptor used by neutrophils for locomotion in extravascular tissue.
Cell adhesion molecules are critically involved in the multistep process of leukocyte recruitment in inflammation. The specific receptors used by polymorphonuclear leukocytes (PMN) for locomotion in extravascular tissue have as yet not been identified. By means of immunofluorescence flow cytometry and laser scanning confocal microscopy, this study demonstrated that surface expression of the alpha(2)beta(1) (VLA-2) integrin, though absent on blood PMN, is induced in extravasated PMN collected from human skin blister chambers, and rat PMN accumulated in the peritoneal cavity after chemotactic stimulation. Intravital time-lapse videomicroscopy was used to investigate chemoattractant-induced PMN locomotion in the rat mesentery in vivo. Local administration of function-blocking monoclonal antibody or peptide recognizing the alpha(2)beta(1) integrin reduced PMN migration velocity in the extravascular tissue by 73% +/- 3% and 70% +/- 10%, respectively (means +/- SD). The distance f-met-leu-phe peptide (fMLP)-stimulated human PMN migrated in a collagen gel in vitro was markedly reduced by treatment with anti-alpha(2) mAbs or peptide, whereas no effect was observed with antibodies or peptides recognizing the alpha(4)beta(1) or alpha(5)beta(1) integrins. Further evidence for a critical role of expression of alpha(2)beta(1) integrin in PMN locomotion in extravascular tissue was obtained in the mouse air pouch model of acute inflammation where chemoattractant-induced PMN recruitment was substantially inhibited by local anti-alpha(2) mAb treatment. Thus, expression of alpha(2)beta(1) integrin on extravasated PMN has been identified and a novel role of this receptor in regulating the extravascular phase of leukocyte trafficking in inflammation has been formulated. (Blood. 2000;95:1804-1809)
Werr
J
J
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Johansson
J
J
Eriksson
E E
EE
Hedqvist
P
P
Ruoslahti
E
E
Lindbom
L
L
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001768:Blister / Q000473:pathology; D002448:Cell Adhesion; D002630:Chemotactic Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology*; D003094:Collagen; D005780:Gelatin; D005782:Gels; D006801:Humans; D007249:Inflammation; D019012:Integrin beta1 / Q000502:physiology; D016023:Integrins / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D018715:Microscopy, Video; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010529:Peritoneal Cavity / Q000166:cytology; D010972:Platelet Activating Factor / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D038981:Receptors, Collagen
D000911:Antibodies, Monoclonal; D002630:Chemotactic Factors; D005782:Gels; D019012:Integrin beta1; D016023:Integrins; D010972:Platelet Activating Factor; D038981:Receptors, Collagen; D009240:N-Formylmethionine Leucyl-Phenylalanine; D005780:Gelatin; D003094:Collagen