Spectrum of extracellular matrix degrading enzymes in normal and malignant T lymphocytes.
Human T cells produce and release fibronectin degrading neutral serine proteases with a molecular weight of 50 kD, 70-80 kD (doublet) and 95 kD and have a cell associated 400 kD fibronectin degrading enzyme. In addition, human T cells produce proteases with m.w. 50, 70-80 kD and 400 kD which degrade laminin. CD 4+ T lymphocytes from a non-malignant cloned human T cell line produce a 92 kD gelatinase (MMP 9) and malignant T cell lines release, in addition to the 92 kD gelatinase, low amounts of a 72 kD gelatinase (MMP 2). Purification of the enzymatic activities using benzamidine sepharose yields a 50 kD and a 70 kD band of which the 50 kD band has fibronectin degrading capacity. The purified enzymes do not react with monoclonal antibodies to various previously characterized proteolytic enzymes present in T cells. T lymphocytes from a non-malignant cloned human T cell line produce high amounts of the 50 and 70-80 kD proteases directly after stimulation with anti-CD 3 monoclonal antibodies whereafter the production of these enzymes declines with time. The expression of the 400 kD fibronectin-degrading protease is downregulated by crosslinking of alpha 4 beta 1-integrin receptors on T cells using monoclonal antibodies. Thus, T lymphocytes produce several matrix degrading enzymes with multiple substrate specificities. The expression of these enzymes is controlled partly by lymphocyte activation signals or by direct signalling via beta 1-integrins.
Hauzenberger
D
D
Department of Clinical Immunology, Umeå University Hospital, Sweden.
Bergström
S E
SE
Klominek
J
J
Sundqvist
K G
KG
D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology; D004790:Enzyme Induction; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005347:Fibroblasts; D005353:Fibronectins / Q000378:metabolism; D018093:Gelatinases / Q000032:analysis; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D019169:Jurkat Cells; D007797:Laminin / Q000378:metabolism; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology; D008213:Lymphocyte Activation; D016410:Lymphoma, T-Cell, Cutaneous / Q000473:pathology; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000032:analysis; D008970:Molecular Weight; D014411:Neoplastic Stem Cells / Q000201:enzymology; D012697:Serine Endopeptidases / Q000032:analysis*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000473:pathology; D013601:T-Lymphocytes / Q000201:enzymology*
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D019012:Integrin beta1; D007797:Laminin; D012697:Serine Endopeptidases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2