CD31/PECAM-1-driven chemokine-independent transmigration of human T lymphocytes.
We assessed the relative contribution of CD31/PECAM-1 (platelet-endothelial cell adhesion molecule-1) to T lymphocyte transmigration by the use of transfected murine fibroblasts stably expressing either the human CD31/PECAM-1 or the intercellular adhesion molecule-1 (CD54/ICAM-1). Unlike CD54/ICAM-1, CD31/PECAM-1 supported migration of activated T cells in the absence of chemokines: most of the migrating lymphocytes were CD31+ and displayed a phenotype corresponding to the naive subpopulation (LFA-1 dull and CD45RA+). Migration of activated T lymphocytes through CD54/ICAM-1+ transfected monolayers could be induced by creating a chemotactic gradient with the chemokine monocyte chemotactic protein-1, and the migrating cells mainly displayed a memory phenotype (LFA-1 bright CD45RO+) under these conditions. Furthermore, we found that in transfected cells CD54/ICAM-1 is uniformly distributed along the apical surface of the cells, while CD31/PECAM-1 is concentrated at the intercellular junctions, suggesting the existence of a haptotactic gradient (i.e. a gradient of substrate- or cell-bound molecules) responsible for T cell migration. This was also confirmed by the finding that monolayers of murine fibroblasts transfected with a CD31/PECAM-1 mutant lacking the cytoplasmic domain (CD31/PECAM-1-delta cyto), which has a reduced tendency to localize at cell-cell contact areas, supported efficient adhesion but were unable to induce migration of activated T cells unless a chemotactic gradient was created. We propose that in lymphocytes, homophilic CD31/PECAM-1 adhesion may be primarily involved in transmigration of naive T cells and that its role is complementary to that of CD54/ICAM-1.
Zocchi
M R
MR
Laboratory of Tumor Immunology, Scientific Institute (IRCCS) San Raffaele, Milan, Italy. zocchim@dibit.hsr.it
Ferrero
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Leone
B E
BE
Rovere
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P
Bianchi
E
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Toninelli
E
E
Pardi
R
R
D016475:3T3 Cells; D000818:Animals; D015214:Antigens, Differentiation, Myelomonocytic / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002465:Cell Movement; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*; D014162:Transfection
D015214:Antigens, Differentiation, Myelomonocytic; D015815:Cell Adhesion Molecules; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011993:Recombinant Fusion Proteins