Laminin isoforms of lymph nodes and predominant role of alpha5-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 alpha3, alpha4, alpha5, beta1, beta2, and gamma1 chains and that the same chains, in addition to alpha2, are found in RFs. In functional studies with laminin isoforms covering all Lm alpha chains, alpha5-laminin (Lm-511) was the most adhesion- and migration-promoting isoform for human blood lymphocytes, followed by alpha3- (Lm-332) and alpha4- (Lm-411) laminins, and the lymphocytes used the alpha6beta1 integrin as the primary receptor for the alpha5-laminin. Moreover, Lm-511 strongly co-stimulated T cell proliferation, and blood lymphocytes were able to secrete alpha4- and alpha5-laminins following stimulation. The LN cell number in laminin alpha4-deficient mice compared with wild-type did not differ significantly. This study demonstrates a predominant role for alpha5-laminin(s) in blood lymphocyte biology and identifies LN laminins and their integrin receptors in blood lymphocytes.
Departments of Odontology, Karolinska Institutet at Huddinge, SE-141 04 Stockholm, Sweden.
Gezahegn
G
Gorfu
Ismo
I
Virtanen
Mika
M
Hukkanen
Veli-Pekka
VP
Lehto
Patricia
P
Rousselle
Ellinor
E
Kenne
Lennart
L
Lindbom
Randall
R
Kramer
Karl
K
Tryggvason
Manuel
M
Patarroyo
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D039121:Integrin alpha6beta1 / Q000235:genetics / Q000378:metabolism; D007797:Laminin / Q000378:metabolism* / Q000502:physiology; D008198:Lymph Nodes / Q000378:metabolism*; D008214:Lymphocytes / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D020033:Protein Isoforms / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism
D039121:Integrin alpha6beta1; D007797:Laminin; D020033:Protein Isoforms; D011994:Recombinant Proteins; C097043:laminin alpha5