A serine proteinase inhibitor produced by an HTLV I virus-transformed human T lymphocyte line.
A previous report from our laboratory indicated that a proteinase inhibitor is produced by rabbit T lymphocytes. We now report that a human T cell line, C91/PL, produces a proteinase inhibitor which inhibits the enzymatic activity of trypsin and kallikrein. This newly identified proteinase inhibitor (LPI 1) did not inhibit the enzymatic activity of four other serine proteinases (thrombin, plasmin, chymotrypsin, or pancreatic elastase), a thiol proteinase (papain), or a carboxyl proteinase (pepsin). Active synthesis of LPI 1 by the C91/PL cell line was shown by the appearance of similar levels of inhibitory activity in sequential cell supernatants, lack of appearance of inhibitor in supernatants of cells killed by heat or sodium azide or of viable cells in the presence of cyclohexamide, and incorporation of a radiolabeled amino acid into newly synthesized inhibitor. Although both the inhibitor of rabbit origin and of human origin are proteins produced by T cells and have similar inhibitory specificity, important differences were observed: LPI 1 is sensitive to boiling and the two inhibitors migrate differently upon electrophoresis in substrate-containing polyacrylamide gel. Furthermore, LPI 1 was produced by a cell line of the T4 phenotype which had been established by in vitro viral transformation of human cord blood lymphocytes with HTLV 1 whereas the inhibitor of rabbit origin was produced by normal splenic T cells. Three other human T cell lines of the T4 phenotype, MOLT-13, KE-37, and HPB-ALL, from patients with acute lymphoblastic leukemia did not produce a proteinase inhibitor. Thus, the production of proteinase inhibitors does not appear to be a general characteristic of human T cell lines nor of the T4 subset. Proteinase inhibitors produced by T cells may have an immunoregulatory role in proteinase-mediated physiological processes.
D007611:Aprotinin / Q000302:isolation & purification* / Q000378:metabolism; D002460:Cell Line; D002472:Cell Transformation, Viral; D017977:Deltaretrovirus / Q000502:physiology*; D010450:Endopeptidases; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors; D011480:Protease Inhibitors; D012697:Serine Endopeptidases; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000378:metabolism*; D014361:Trypsin Inhibitors / Q000302:isolation & purification
D011480:Protease Inhibitors; D014361:Trypsin Inhibitors; D007611:Aprotinin; D010450:Endopeptidases; D007610:Kallikreins; D012697:Serine Endopeptidases