Extracellular matrix induces tumour necrosis factor-alpha secretion by an interaction between resting rat CD4+ T cells and macrophages.
T lymphocytes and macrophages (M phi) have been seen to accumulate at sites of lesions in blood vessel walls, suggesting that these cells may contribute to the pathogenesis of inflammatory reactions. Tumour necrosis factor-alpha (TNF-alpha), a cytokine produced by both M phi and T lymphocytes, plays a major role in inflammatory reactions, blood vessel formation, thrombosis and atherosclerosis. We now report that secretion of TNF-alpha by cloned CD4+ rat T cells, and to a lesser degree by peripheral T cells, and M phi can be induced in vitro in the absence of antigen, in a major histocompatibility complex (MHC) class II-independent manner by integrin-mediated recognition of immobilized components of extracellular matrix such as fibronectin and laminin; the secretion of TNF-alpha by the interacting resting cells on fibronectin was partially abrogated by the presence of the Arg-Gly-Asp (RGD)-containing amino acid sequence. This T cell-M phi interaction involves CD2 and CD4 molecules and requires a signal transduced in the T cells by a protein tyrosine kinase. Thus, a multicellular interaction with extracellular matrix protein exposed as a consequence of vascular wall injury can serve to signal the secretion of TNF-alpha which induces the recruitment of additional immune cells to the developing lesion.
Hershkoviz
R
R
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Gilat
D
D
Miron
S
S
Mekori
Y A
YA
Aderka
D
D
Wallach
D
D
Vlodavsky
I
I
Cohen
I R
IR
Lider
O
O
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D018801:CD2 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000276:immunology*; D005353:Fibronectins / Q000276:immunology; D007797:Laminin / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011971:Receptors, Immunologic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007797:Laminin; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha