Human B lymphocytes synthesize the 92-kDa gelatinase, matrix metalloproteinase-9.
Matrix metalloproteinases (MMPs) are involved in the remodeling of connective tissue as well as in disease states associated with acute and chronic inflammation or tumoral metastatic processes. Despite detailed and extensive studies of the mechanisms of lymphocyte extravasation, remarkably little is known about the expression and regulation of metalloproteinases involved in the migratory process. By using zymography and reverse transcription-polymerase chain reaction experiments, we have demonstrated that Epstein-Barr virus-immortalized B lymphocytes are able to secrete a 92-kDa metalloproteinase with gelatinolytic activity which has been purified and identified as being MMP-9. Moreover, the tissue inhibitor of metalloproteinase was shown to be constitutively expressed by the B cells. The expression of 92-kDa gelatinase is mediated by cytokines, growth factors, lipopolysaccharide, concanavalin A, and the tumor promotor phorbol 12-myristate 13-acetate. Time dependence activity increased rapidly up to 24 h of incubation with lipopolysaccharide or concanavalin A stimulation while it requires a delay and more time to have an optimum effect when cytokines were the stimulating agents; transforming growth factor-beta abolished 92-kDa gelatinase production. Both staurosporine and wortmannin are inductive stimuli, and the level of MMP-9 secreted into the media is greater than that observed with other agents except concanavalin A. Elicitation of the chemotactic migration of B cells through a model basement membrane by lipopolysaccharide was shown to be correlated with gelatinase expression and inhibited by 7 mM captopril. Our study indicates that Epstein-Barr virus-B lymphocytes express 92-kDa gelatinase, the production of which can be modified by a variety of physiological and pharmacological signals which have been shown to differ according to the cell type.
Trocmé
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UPR ES EA 2019, GREPI, Laboratoire d'Enzymologie, CHU Albert Michallon, 38043 Grenoble Cedex, France.
Gaudin
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Berthier
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S
Barro
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Zaoui
P
P
Morel
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F
D000730:Androstadienes / Q000494:pharmacology; D001402:B-Lymphocytes / Q000201:enzymology*; D002216:Captopril / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D017364:Collagenases / Q000378:metabolism*; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9; D012333:RNA, Messenger / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014170:Transformation, Genetic / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D000077191:Wortmannin
D000730:Androstadienes; D016207:Cytokines; D006133:Growth Substances; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D003208:Concanavalin A; D002216:Captopril; D017364:Collagenases; D020780:Matrix Metalloproteinase 9; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D000077191:Wortmannin