Integrin-dependent role of human T cell matrix metalloproteinase activity in chemotaxis through a model basement membrane.
Human T lymphoblastoma cells of the CD4+ 8+ Tsup-1 line, that express alpha 4 and alpha 5 but not alpha 6 integrins of the beta 1 family, and CD4+ human blood T cells bind vasoactive intestinal peptide (VIP) with high affinity, leading to increased adherence, secretion of matrix metalloproteinases (MMPs), and chemotaxis. VIP-enhanced adherence of T cells to fibronectin was inhibited significantly by neutralizing monoclonal antibodies to beta 1 > alpha 4 > > alpha 5, but not to alpha 6. Antibodies to beta 1 and alpha 4 suppressed to a similarly significant extent VIP stimulation of both MMP-dependent T cell chemotaxis through fibronectin-enriched Matrigel and T cell degradation of 3H-type IV collagen in the Matrigel, without affecting VIP-evoked secretion of MMP by suspensions of T cells. The lesser inhibition of VIP-enhanced adherence of T cells to fibronectin by anti-alpha 5 antibody, than antibodies to beta 1 or alpha 4 chains, was associated with lesser or no suppression of MMP-dependent T cell chemotaxis through Matrigel and T cell degradation of type IV collagen in the Matrigel in response to VIP. Specific beta 1 integrins thus mediate interactions of stimulated T cells with basement membranes, including adherence, localized digestion by MMPs, and chemotactic passage, that promote entry of T cells into extravascular tissues.
Xia
M
M
Department of Medicine and Microbiology-Immunology, Howard Hughes Medical Institute, University of California, San Francisco 94143-0711, USA.
Sreedharan
S P
SP
Dazin
P
P
Damsky
C H
CH
Goetzl
E J
EJ
D019138:Antibodies, Blocking / Q000276:immunology; D001485:Basement Membrane / Q000201:enzymology*; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology*; D016827:CD8 Antigens / Q000378:metabolism; D002448:Cell Adhesion; D002633:Chemotaxis; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000201:enzymology*; D005353:Fibronectins / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D019012:Integrin beta1 / Q000276:immunology / Q000502:physiology*; D008666:Metalloendopeptidases / Q000502:physiology*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology*; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
D019138:Antibodies, Blocking; D015704:CD4 Antigens; D016827:CD8 Antigens; D005353:Fibronectins; D019012:Integrin beta1; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D003094:Collagen; D008666:Metalloendopeptidases