Laminin isoforms of lymph nodes and predominant role of 5- laminin(s) in adhesion and migration of blood lymphocytes

During extravasation and within lymph nodes (LNs), blood lymphocytes interact with laminins (Lms), major components of vascular basement membranes (BMs) and of reticular fibers (RFs), a fibrillar extracellular matrix. However, the identity and role of these laminin isoform(s) are poorly known. By using confocal microscopy examination of human LNs, we show that BMs of high endothelial venules (HEVs) express laminin 3, 4, 5, 1, 2, and 1 chains and that the same chains, in addition to 2, are found in RFs. In functional studies with laminin isoforms covering all Lm chains, 5-laminin (Lm-511) was the most adhesionand migration-promoting isoform for human blood lymphocytes, followed by 3(Lm-332) and 4(Lm-411) laminins, and the lymphocytes used the 6 1 integrin as the primary receptor for the 5-laminin. Moreover, Lm-511 strongly costimulated T cell proliferation, and blood lymphocytes were able to secrete 4and 5-laminins following stimulation. The LN cell number in laminin 4-deficient mice compared with wild-type did not differ significantly. This study demonstrates a predominant role for 5-laminin(s) in blood lymphocyte biology and identifies LN laminins and their integrin receptors in blood lymphocytes. J. Leukoc. Biol. 84: 000–000; 2008.