1. Laminin isoforms of lymph nodes and predominant role of {alpha}5-laminin(s) in adhesion and migration of blood lymphocytes
- Author
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Gorfu, G., Virtanen, I., Hukkanen, M., Lehto, Vp, Rousselle, P., Kenne, E., Lindbom, L., Kramer, R., Tryggvason, K., Patarroyo, M., and Deleage, Gilbert
- Subjects
[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology - Abstract
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 Lm isoform(s) are poorly known. By using confocal microscopy examination of human LNs, we show that BMs of high endothelial venules express Lmalpha3, -alpha4, -alpha5, -beta1, -beta2, and -gamma1 chains and that the same chains, in addition to alpha2, are found in RFs. In functional studies with Lm isoforms covering all Lmalpha chains, Lmalpha5 (Lm-511) was the most adhesion- and migration-promoting isoform for human blood lymphocytes, followed by Lmalpha3 (Lm-332) and Lmalpha4 (Lm-411), and the lymphocytes used the alpha6beta1 integrin (INT) as the primary receptor for the Lmalpha5. Moreover, Lm-511 strongly costimulated T cell proliferation, and blood lymphocytes were able to secrete Lmalpha4 and -alpha5 following stimulation. The LN cell number in Lmalpha4-deficient mice compared with wild-type did not differ significantly. This study demonstrates a predominant role for Lmalpha5 in blood lymphocyte biology and identifies LN Lms and their INT receptors in 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 Lm isoform(s) are poorly known. By using confocal microscopy examination of human LNs, we show that BMs of high endothelial venules express Lmalpha3, -alpha4, -alpha5, -beta1, -beta2, and -gamma1 chains and that the same chains, in addition to alpha2, are found in RFs. In functional studies with Lm isoforms covering all Lmalpha chains, Lmalpha5 (Lm-511) was the most adhesion- and migration-promoting isoform for human blood lymphocytes, followed by Lmalpha3 (Lm-332) and Lmalpha4 (Lm-411), and the lymphocytes used the alpha6beta1 integrin (INT) as the primary receptor for the Lmalpha5. Moreover, Lm-511 strongly costimulated T cell proliferation, and blood lymphocytes were able to secrete Lmalpha4 and -alpha5 following stimulation. The LN cell number in Lmalpha4-deficient mice compared with wild-type did not differ significantly. This study demonstrates a predominant role for Lmalpha5 in blood lymphocyte biology and identifies LN Lms and their INT receptors in blood lymphocytes.
- Published
- 2008