Plasmin Is a Specific Stimulus of the 5-Lipoxygenase Pathway of Human Peripheral Monocytes

Summary

The objective of this study was to characterize the plasmin-induced stimulation of leukotriene (LT) B4 biosynthesis in human peripheral monocytes (PM). Plasmin up to 175 × 10^-3 CTA U/ml triggers a concentration-dependent release of 5-lipoxygenase-derived LTB4 while release of the cyclooxygenase products thromboxane (TX) B₂ and prostaglandin (PG) E₂ remained unaffected. The stimulatory effect appeared to be specific in as much as 1) it was found in PM, but not in polymorphonuclear neutrophils (PMN), 2) it requires the lysine binding sites of plasmin molecule since it was inhibited by the lysine analogues 6-aminohexanoic acid (6-AHA) and trans-4(aminometh-yl)cyclohexane-l-carboxylic acid (t-AMCA), 3) the intact catalytic center of plasmin is required since neither plasminogen nor catalytic center-blocked plasmin share the stimulatory effect of active plasmin, 4) other serine proteases such as a-chymotrypsin, human neutrophil elastase and cathepsin G did not stimulate release of detectable amounts of LTB4 from PM. In addition, catalytic center-blocked plasmin antagonized the stimulatory effect of active plasmin. Plasmin-mediated monocyte activation apparently proceeds via a pertussis toxin-sensitive G protein. Plasmin did not increase inositol (1,4,5) trisphosphate levels, but a time- and concentration-dependent stimulation of cyclic GMP formation was observed. The data show that plasmin is a specific stimulus for human peripheral monocytes. Plasmin may be an important link between the coagulation cascade and inflammatory reactions.

• References

• 1 Kozin F, Cochrane CG. The contact activation system of plasma. Biochemistry and pathophysiology. In: Inflammation: Basic Principles and Clinical Correlates. Second Edition. Gallin JI, Goldstein IM, Snyderman R, eds. Raven Press, New York, NY 1992: 103-121
• 2 Kaplan AP, Silverberg M. The coagulation-kinin pathway of human plasma. Blood 1987; 70: 1-15
• 3 Simmet Th, Luck W. Radioreceptor assay for leukotriene B4. Use for determination of leukotriene B4 formation by whole human blood. Eicosanoids 1988; 1: 107-110
• 4 Simmete Th, Luck W. Clotting of whole human blood induces cysteinyl-leukotriene formation. Thromb Res 1989; 54: 423-433
• 5 Simmet Th, Weide I. Thromboxane and cysteinyl-leukotriene formation are differentially activated in spontaneously clotting whole human blood in vitro. Thromb Res 1991; 62: 249-261
• 6 Weide I, Simmet Th. Leukotriene formation by peripheral monocytes in contact-activated human blood. Thromb Res 1993; 71: 185-192
• 7 Weide I, Romisch J, Simmet Th. Contact activation triggers stimulation of the monocyte 5-lipoxygenase pathway via plasmin. Blood 1994; 83: 1941-1951
• 8 Silverstein RL, Friedlander Jr RJ, Nicholas RL, Nachman RL. Binding of Lys-plasminogen to monocytes/macrophages. J Clin Invest 1988; 82: 1948-1955
• 9 Palmere S, Wakelam MJO. Mass measurement of inositol 1,4,5-trisphos-phate using a specific binding assay. In: Methods in Inositide Research. Irvine RF, ed. Raven Press, New York, NY 1990: 127-134
• 10 Nibbering PH, Zomerdijk TPL, van Haastert PJM, van Furth R. A competition binding assay for determination of the inositol (1,4,5)-trisphosphate content of human leucocytes. Biochem Biophys Res Commun 1990; 170: 755-762
• 11 Friberger P, Knos M, Gustavsson S, Aurell L, Claeson G. Methods for determination of plasmin, antiplasmin and plasminogen by means of substrate S-2251. Haemostasis 1978; 7: 138-145
• 12 Lu H, Soria C, Li H, Soria J, Lijnen HR, Perrot JY, Caen JP. Role of active center and lysine binding sites of plasmin in plasmin-induced platelet activation and disaggregation. Thromb Haemost 1991; 65: 67-72
• 13 Verghese MW, Smith CD, Charles LA, Jakoi L, Synderman R. A guanine nucleotide regulatory protein controls polyphosphoinositide metabolism, Ca2+ mobilization, and cellular responses to chemoattractants in human monocytes. J Immunol 1986; 137: 271-275
• 14 Sozzani S, Luini W, Molino M, Jilek P, Bottazzi B, Cerletti C, Matsushima K, Mantovani A. The signal transduction pathway involved in the migration induced by a monocyte chemotactic cytokine. J Immunol 1991; 147: 2215-2221
• 15 Pliska V. Models to explain dose-response relationships that exhibit a downturn phase. TIPS 1994; 15: 178-181
• 16 Rovati EG, Nicosia S. Lower efficacy: Interaction with an inhibitory receptor or partial agonism. TIPS 1994; 15: 140-144
• 17 Kenakin T. Agonist-receptor efficacy I: Mechanisms of efficacy and receptor promiscuity. TIPS 1995; 16: 188-192
• 18 Snyderman R, Uhing RJ. Chemoattractant stimulus-response coupling. In: Inflammation: Basic Principles and Clinical Correlates. Second Edition. Gallin JI, Goldstein IM, Snyderman R, eds. Raven Press, New York, NY 1992: 421-439
• 19 Castellino FJ, Sodetz JM. Rabbit plasminogen and plasmin isozymes. Methods Enzymol 1976; 45: 273-286
• 20 Bar-Shavit R, Kahn A, Fenton JW, Wilner GD. Chemotactic response of monocytes to thrombin. J Cell Biol 1983; 96: 282-285
• 21 Bar-Shavit R, Kahn AL, Mann KG, Wilner GD. Identification of a thrombin sequence with growth factor activity on macrophages. Proc Natl Acad Sci USA 1986; 83: 976-980
• 22 Weide I, Simmet Th. Novel chemotactic activation specific for human peripheral monocytes. Inflammation Res 1995; (Suppl. 03) Suppl 44: S246
• 23 Schafer AI, Adelman B. Plasmin inhibition of platelet function and of arachidonic acid metabolism. J Clin Invest 1985; 75: 456-461
• 24 Schafer AI, Maas AK, Ware JA, Johnson PC, Rittenhouse SE, Salzman EW. Platelet protein phosphorylation, elevation of cytosolic calcium, and inositol phospholipid breakdown in platelet activation induced by plasmin. J Clin Invest 1986; 78: 73-79
• 25 Pawlowski NA, Kaplan G, Hamill AL, Cohn ZA, Scott WA. Arachidonic acid metabolism by human monocytes. J Exp Med 1983; 158: 393-412
• 26 Balter MS, Toews GB, Peters-Golden M. Different patterns of arachidonate metabolism in autologous human blood monocytes and alveolar macrophages. J Immunol 1989; 142: 602-608
• 27 Goppelt-Struebe M. Regulation of prostaglandin endoperoxide synthase (Cyclooxygenase) isoenzyme expression. Prostaglandins Leukotrienes Essent Fatty Acids 1995; 52: 213-222
• 28 Marshall LA, Bolognese B, Roshak A. Human monocyte phospholipase A2 enzymes regulate distinct aspects of arachidonic acid metabolism. Inflammation Res 1995; 44 (Suppl. 03) Suppl S258
• 29 Ryan TJ, Lai L, Malik AB. Plasmin generation induces neutrophil aggregation: dependence on the catalytic and lysine binding sites. J Cell Physiol 1992; 151: 255-261
• 30 Chang WC, Shi GY, Chow YH, Chang LC, Hau JS, Lin MT, Jen CJ, Wing LYC, Wu HL. Human plasmin induces a receptor-mediated arachidonate release coupled with G proteins in endothelial cells. Am J Physiol 1993; 264: C271-C281
• 31 Miles LA, Dahlberg CM, Plescia J, Felez J, Kato K, Plow EF. Role of cell-surface lysines in plasminogen binding to cells: identification of a-enolase as a possible candidate plasminogen receptor. Biochemistry 1991; 30: 1682-1691
• 32 Miles LA, Plow EF. Receptor mediated binding of the fibrinolytic components, plasminogen and urokinase, to peripheral blood cells. Thromb Haemost 1987; 58: 936-942
• 33 Miles LA, Plow EF. Plasminogen receptors: Ubiquitous sites for cellular regulation of fibrinolysis. Fibrinolysis 1988; 2: 61-71
• 34 Felez J, Miles LA, Plescia J, Plow EF. Regulation of plasminogen receptor expression on human monocytes and monocytoid cell lines. J Cell Biol 1990; 111: 1673-1683
• 35 Hajjar KA. Cellular receptors in the regulation of plasmin generation. Thromb Haemost 1995; 74: 294-301
• 36 Miles LA, Dahlberg CM, Levin EG, Plow EF. Gangliosides interact directly with plasminogen and urokinase and may mediate binding of these fibrinolytic components to cells. Biochemistry 1989; 28: 9337-9343
• 37 Falcone DJ, Borth W, Mathew J, Guevara C, Hajjar KA. Annexin II is a plasminogen receptor on THP-1 macrophages. FASEB J 1995; 9: 2388
• 38 Vu TKH, Hung DT, Wheaton VI, Coughlin SR. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell 1991; 64: 1057-1068
• 39 Vu TKH, Wheaton VI, Hung DT, Charo I, Coughlin SR. Domains specifying thrombin-receptor interaction. Nature 1991; 353: 674-677
• 40 Kitagawa S, Takaku F, Sakamoto S. Evidence that proteases are involved in superoxide production by human polymorphonuclear leukocytes and monocytes. J Clin Invest 1980; 65: 74-81
• 41 King CH, Goralnik CH, Kleinhenz PJ, Marino JA, Sedor JR, Mahmoud AF. Monoclonal antibody characterization of a chymotrypsin-like molecule on neutrophile membrane associated with cellular activation. J Clin Invest 1987; 79: 1091-1098
• 42 Kilpatrick L, Johnson JL, Nickbarg EB, Wang ZM, Clifford TF, Banach M, Cooperman BS, Douglas SD, Rubin H. Inhibition of human neutrophil superoxide generation by oq-antichymotrypsin. J Immunol 1991; 146: 2388-2393
• 43 Camussi G, Tetta C, Bussolino F, Baglioni C. Synthesis and release of platelet-activating factor is inhibited by plasma a j-proteinase inhibitor or a,-antichymotrypsin and is stimulated by proteinases. J Exp Med 1988; 168: 1293-1306
• 44 Camussi G, Tetta C, Bussolino F, Baglioni C. Tumor necrosis factor stimulates human neutrophils to release leukotriene B4 and platelet-activating factor. Eur J Biochem 1989; 182: 661-666
• 45 Berridge MJ, Irvine RF. Inositol phosphates and cell signalling. Nature 1989; 341: 197-205
• 46 Smith CD, Cox CC, Synderman R. Receptor-coupled activation of phosphoinositide-specific phospholipase C by an N protein. Science 1986; 232: 97-100
• 47 Belenky SN, Robbins RA, Rubinstein I. Nitric oxide synthase inhibitors attenuate human monocyte chemotaxis in vitro. J Leukocyte Biol 1993; 53: 498-503
• 48 Kaplan S, Billiar T, Curran RD, Zdziarski UE, Simmons RL, Basford RE. Inhibition of chemotaxis with NG-monomethyl-L-arginine: A role for cyclic GMP. Blood 1989; 74: 1885-1887
• 49 Lam BK, Austen KF. Leukotrienes. Biosynthesis, release, and actions. In: Inflammation: Basic Principles and Clinical Correlates. Second Edition. Gallin JI, Goldstein IM, Snyderman R, eds. Raven Press, New York, NY 1992: 139-147
• 50 Migliorisi G, Folkes E, Pawlowski N, Cramer EB. In vivo studies of human monocyte migration across endothelium in response to leukotriene B4 and f-Met-Leu-Phe. Am J Pathol 1987; 127: 157-167