Introduction
The subject of this study was to identify the function of integrin receptors in PMN locomotion.
Methods
Chemoattractant-induced PMN locomotion was analyzed in vivo using intravital time-lapse videomicroscopy in the rat mesentery and in vitro using gels of collagen (type 1). Chemotactic PMN accumulation was also analyzed in vivo using the mouse air pouch model. Immunofluorescence flow cytometry and laser scanning confocal microscopy were used to demonstrate dynamic changes in integrin expression in association with PMN extravasation. Extravasated human PMN were obtained using the skin blister chamber technique.
Results
Surface expression of a2b1 integrin, while absent on blood PMN, was induced in extravasated PMN collected from human skin blister chambers. Antibody blockade of a2b1 integrin reduced PMN migration velocity in the rat mesentery by 73 ± 3 % (mean ± SD). Likewise, the migration distance of human PMN in collagen gels was markedly reduced by treatment with anti-a2 antibodies. Similar observations were obtained from the mouse air pouch. Antibodies against a4b1 or a5b1 integrins were ineffective in inhibiting PMN locomotion.
Conclusions
We identify expression of a2b1 integrin on extravasated PMN and a novel role of this receptor in regulating the extravascular phase of PMN recruitment to tissues in inflammation.
References
Werr, J.et al.(1998) beta1 integrins are critically involved in neutrophil locomotion in extravascular tissue In vivo. J.Exp.Med. 187(12), 2091-2096.
Werr, J.et al.Integrin a2b1 (VLA-2) is a principal receptor utilized by neutrophils for locomotion in extravascular tissue. Blood 2000;95(5), 1804-1809.