Secondary lymphoid-tissue chemokine (SLC) stimulates integrin alpha 4 beta 7-mediated adhesion of lymphocytes to mucosal addressin cell adhesion molecule-1 (MAdCAM-1) under flow.
The attachment of leukocytes to the endothelium is a multistep process that depends upon a very rapid increase in the adhesive activity of leukocyte integrins. A pertussis toxin-sensitive pathway stimulates integrin-dependent lymphocyte adhesion to Peyer's patch high endothelial venules in vivo, but the factors responsible for activating this pathway have not been identified previously. We now report that secondary lymphoid-tissue chemokine (SLC) (also known as 6Ckine, Exodus-2, and thymus-derived chemotactic agent 4), a recently described CC chemokine that is expressed in Peyer's patches and lymph nodes, rapidly activates integrin-mediated lymphocyte adhesion. Immobilized SLC increased the adhesion of HUT-78 T cells and human PBLs to mucosal addressin cell adhesion molecule-1, a protein that is expressed on Peyer's patch and mesenteric lymph node high endothelial venules. This effect of SLC was seen in both static and flow chamber adhesion assays, was mediated by integrin alpha 4 beta 7, and was inhibited by pertussis toxin. The other CC chemokines tested did not increase adhesion to mucosal addressin cell adhesion molecule-1. SLC had a greater effect on naive CD4+ T cells than on memory CD4+ T cells; CD8+ T cells, B cells, and NK cells were also responsive to SLC. SLC is likely to play an important role in regulating the recruitment of lymphocytes to Peyer's patches and lymph nodes.
Lung Biology Center, Department of Medicine, University of California, San Francisco 94143, USA.
R K
RK
Pachynski
S W
SW
Wu
M D
MD
Gunn
D J
DJ
Erle
D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D015815:Cell Adhesion Molecules; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000502:physiology*; D015194:Diffusion Chambers, Culture; D006801:Humans; D007136:Immunoglobulins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D016023:Integrins / Q000502:physiology*; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000276:immunology*; D009088:Mucoproteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D037342:Pertussis Toxin; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
C515478:CCL21 protein, human; D015815:Cell Adhesion Molecules; D054421:Chemokine CCL21; D019742:Chemokines, CC; D007136:Immunoglobulins; D016023:Integrins; C504265:MADCAM1 protein, human; D009088:Mucoproteins; D011993:Recombinant Fusion Proteins; D010566:Virulence Factors, Bordetella; C071777:integrin alpha4beta7; D037342:Pertussis Toxin