Leukocyte transmigration is decreased in mice lacking the laminin alpha‐4 chain

Abstract

Leukocyte extravasation is a critical event in inflammatory reactions. In order for leukocytes to penetrate the vessel wall they need to sequentially interact with the endothelial lining and the perivascular basement membrane (BM). Laminin matrix proteins (laminins 8 and 10) are major constituents of the vascular BM. The laminin alpha-4 chain is a component of laminin-8, and serves roles as a structure protein and as a signaling molecule. The object of this study was to investigate the importance of laminin alpha-4 chain containing laminins in leukocyte transmigration. Intravital microscopy was used to visualize leukocyte adhesion and transmigration in mouse cremasteric venules of laminin alpha-4 chain deficient (Lam−/−) and wild-type mice. The cremaster muscle was stimulated with platelet activating factor (PAF) and readings were taken at early (15 min) and late (60 min) time points of stimulation. Leukocyte transmigration, but not adhesion to the endothelial lining, was markedly suppressed in Lam−/− compared to wild-type mice at 60 min indicating an impaired ability to penetrate the endothelial BM. The results suggest an essential role of interaction with vascular laminin-8 for efficient migration through the vessel wall. Supported by grants from the Swedish Research Council and the Swedish Heart-Lung Foundation.