Enhanced Response to Chemotactic Activation of Polymorphonuclear Leukocytes from Patients with Heart Valve Replacement

Summary

Artificial surfaces activate blood components. Since anticoagulant and antiplatelet therapy fail to abolish thromboembolic complications in patients with mechanical heart valve replacement (MHVR), other mechanisms might contribute to switch on a thrombotic event. We therefore investigated the reactivity to chemotactic activation of PMN from patients with MHVR. PMN responses were analyzed in 3 groups: 130 patients with MHVR and oral anticoagulant therapy, with or without aspirin, 57 patients on a comparable antithrombotic regimen, but without MHVR and 50 healthy subjects. In vitro studies showed that the release of cathepsin G and elastase from fMLP-stimulated PMN was significantly higher in the MHVR group, the leukocyte content of α₁-antitrypsin (an inhibitor of both enzymes) being similar in all three groups. CD1 lb expression after stimulation with fMLP was also significantly higher on PMN from MHVR patients than from control patients or healthy volunteers, while PMN CD 11b basal expression was similar in all three groups. This increased PMN response in vitro in the absence of an obvious activation in vivo, may reflect a modified reactivity of circulating PMN passing through the artificial valves. Increased reactivity to local stimuli might allow PMN to participate in thrombus formation, despite conventional antithrombotic therapy.

• References

• 1 Ibrahim M, O’Kane H, Cleland J, Gladstone D, Sarsam M, Patterson C. The St. Jude Medical prothesis. A thirteen-year experience. J Thorac Cardiovasc Surg 1994; 108: 221-230
• 2 Turpie AG, Gent M, Laupacis A, Latour Y, Gunstensen J, Basile F, Klimek M, Hirsh J. A comparison of aspirin with placebo in patients treated with warfarin after heart valve replacement. N Engl J Med 1993; 329: 524-329
• 3 Altman R, Rouvier J, Gurfinkel E, D’Ortencio O, Manzanel R, de LaFuente L, Favaloro RG. Comparison of two levels of anticoagulant therapy in patients with substitute heart valves. J Thorac Cardiovasc Surg 1991; 101: 427-431
• 4 Edmunds Jr LH. Thrombotic and bleeding complications of prosthetic heart valves. Ann Thorac Surg 1987; 44: 430-445
• 5 Chenoweth DE, Cooper SW, Hugli TE, Stewart RW, Blackstone EH, Kirklin JW. Complement activation during cardiopulmonary bypass. Evidence for generation of C3a and C5a anaphylatoxins. N Engl J Med 1981; 304: 497-503
• 6 Wachtfogel YT, Kucich U, Greenplate J, Gluszko P, Abrams W, Weinbaum G, Wenger RK, Rucinski B, Niewiarowski S, Edmunds Jr LH, Colman RW. Human neutrophil degranulation during extracorporeal circulation. Blood 1987; 69: 324-330
• 7 Nathan CF. Neutrophil activation on biological surfaces. Massive secretion of hydrogen peroxide in response to products of macrophages and lymphocytes. J Clin Invest 1987; 80: 1550-1560
• 8 Stahl RF, Fisher CA, Kucich U, Weinbaum G, Warsaw DS, Stenach N, O’Connor C, Addonizio VP. Effects of simulated extracorporeal circulation on human leukocyte elastase release, superoxide generation, and procoagulant activity. J Thorac Cardiovasc Surg 1991; 101: 230-239
• 9 Lowe GDO, Machado SG, Krol WF, Barton BA, Forbes CD. White blood cell count and haematocrit as predictors of coronary recurrence after myocardial infarction. Thromb Haemost 1985; 54: 700-703
• 10 Ernst E, Hammerschmidt DE, Bagge U, Matrai A, Dormandy JA. Leukocytes and the risk of ischemic diseases. JAMA 1987; 257: 2318-2324
• 11 Mehta JL, Nicolini FA, Donnelly WH, Nichols WW. Platelet-leukocyte-endothelial interactions in coronary artery disease. Am J Cardiol 1992; 69: 8B-13B
• 12 Mehta J, Dinerman J, Mehta P, Saldeen TG, Lawson D, Donnelly WH, Wallin R. Neutrophil function in ischemic heart disease. Circulation 1989; 79: 549-556
• 13 Mazzone A, De ServiS, Ricevuti G, Mazzucchelli I, Fossati G, Pasotti D, Bramucci E, Angoli L, Marsico F, Specchia G, Notario A. Increased expression of neutrophil and monocyte adhesion molecules in unstable coronary artery disease. Circulation 1993; 88: 358-363
• 14 Grau AJ, Berger E, Sung KL, Schmid-Schonbein GW. Granulocyte adhesion, deformability, and superoxide formation in acute stroke. Stroke 1992; 23: 33-39
• 15 Del MaschioA, Evangelista V, Rajtar G, Chen ZM, Cerletti C, de GaetanoG. Platelet activation by polymorphonuclear leukocytes exposed to chemotactic agents. Am J Physiol 1990; 258: H870-H879
• 16 Totani L, Piccoli A, Pellegrini G, Di SantoA, Lorenzet R. Polymorphonuclear leukocytes enhance release of growth factors by cultured endothelial cells. Arterioscler Thromb 1994; 14: 125-132
• 17 Allen DH, Tracy PB. Human coagulation factor V is activated to the functional cofactor by elastase and cathepsin G expressed at the monocyte surface. J Biol Chem 1995; 270: 1408-1415
• 18 Altieri DC, Edgington TS. The saturable high affinity association of factor X to ADP-stimulated monocytes defines a novel function of the Mac-1 receptor. J Biol Chem 1988; 263: 7007-7015
• 19 Altieri DC, Bader R, Mannucci PM, Edgington TS. Oligospecificity of the cellular adhesion receptor MAC-1 encompasses an inducible recognition specificity for fibrinogen. J Cell Biol 1988; 107: 1893-1900
• 20 Henderson LM, Figueroa CD, Muller-Esterl W, Bhoola KD. Assembly of contact-phase factors on the surface of the human neutrophil membrane. Blood 1994; 84: 474-482
• 21 Entman ML, Ballantyne CM. Inflammation in acute coronary syndromes. Circulation 1993; 88: 800-803
• 22 Neri SemeriGG, Abbate R, Gori AM, Attanasio M, Martini F, Giusti B, Dabizzi P, Poggesi L, Modesti PA, Trotta F, Rostagno C, Boddi M, Gensini GF. Transtient intermittent lymphocyte activation is responsible for the instability of angina. Circulation 1992; 86: 790-797
• 23 Evangelista V, Rajtar G, de GaetanoG, White JG, Cerletti C. Platelet activation by fMLP-stimulated polymorphonuclear leukocytes: the activity of cathepsin G is not prevented by antiproteinases. Blood 1991; 77: 2379-2388
• 24 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin Phenol reagent. J Biol Chem 1981; 193: 265-272
• 25 Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680
• 26 Pumphrey CW, Dawes J. Platelet alpha granules depletion: findings in patients with prosthetic heart valves and following cardiopulmonary bypass surgery. Thromb Res 1983; 30: 257-264
• 27 Salzman EW, Merril EW, Kent KC. Interaction of blood with artificial surfaces. In: Colman RW, Hirsh J, Marder VJ, Edwin J, Salzman EW. (eds) Hemostasis and thrombosis: basic principles and clinical practice. Philadelphia; Lippincott Co: 1992. pp 1469-1485
• 28 Sturzenegger M, Beer JH, Rihs F. Monitoring combined antithrombotic treatments in patients with prosthetic heart valves using transcranial Doppler and coagulation markers. Stroke 1995; 26: 63-69
• 29 Craddock PR, Fehr J, Brigham KL, Kronenberg RS, Jacob HS. Complement and leukocyte-mediated pulmonary dysfunction in hemodialysis. N Engl J Med 1977; 296: 769-774
• 30 Carlos TM, Harlan JM. Leukocyte-endothelial adhesion molecules. Blood. 1994; 84: 2068-2101
• 31 Altieri DC. Coagulation assembly on leukocytes in trasmembrane signaling and cell adhesion. Blood 1993; 81: 569-579
• 32 Halvorsen H, Olsen JO, Osterud B. Granulocytes enhance LPS-induced tissue factor activity in monocytes via an interaction with platelets. JLeukoc Biol 1993; 54: 275-282
• 33 Palabrica T, Lobb R, Furie BC, Aronovitz M, Benjamin C, Hsu YM, Sajer SA, Furie B. Leukocyte accumulation promoting fibrin deposition is mediated in vivo by P-selectin on adherent platelets. Nature 1992; 359: 848-851
• 34 Cerletti C, Evangelista V, Molino M, de GaetanoG. Platelet activation by polymorphonuclear leukocytes: role of cathepsin G and P-selectin. Thromb Haemost 1995; 74: 218-223
• 35 Weksler BB, Jaffe EA, Brower MS, Cole OF. Human leukocyte cathepsin G specifically suppress thrombin-induced prostacyclin production in human endothelial cells. Blood 1989; 74: 1627-1634
• 36 Chignard M, Balloy V, Renesto P. Release of von Willebrand factor by HUVEC incubated with human leukocyte elastase. Thromb Haemost 1993; 69: 1127
• 37 Pintucci G, Iacoviello L, Castelli MP, Amore C, Evangelista V, Cerletti C, Donati MB. Cathepsin G-induced release of PAI-1 in the culture medium of endothelial cells: a new thrombogenic role for polymorphonuclear leukocytes?. J Lab Clin Med 1993; 122: 69-79
• 38 Wu K, Urano T, Ihara H, Takada Y, Fujie M, Shikimory M, Hashimoto K, Takada A. The cleavage and inactivation of plasminogen activator inhibitor type 1 by neutrophil elastase: the evaluation of its physiologic relevance in fibrinolysis. Blood 1995; 86: 1056-1061
• 39 Selak MA, Chignard M, Smith JB. Cathepsin G is a strong platelet agonist released by neutrophils. Biochem J 1988; 251: 293-299
• 40 Mason DY, Cramer EM, Masse JM, Crystal R, Bassot JM, Breton-Gorius J. Alpha 1-antitrypsin is present within the primary granules of human polymorphonuclear leukocytes. Am J Patho 1991; 139: 623-628
• 41 Thomas RM, Nauseef WM, Iyer SS, Peterson MW, Stone PJ, Clark RA. A cytosolic inhibitor of human neutrophil elastase and cathepsin G. J Leukoc Biol 1991; 01: 568-579
• 42 Lee CS, Chandran KB. Instantaneous back flow through peripheral clearence of Medtronic Hall tilting disk valve at the moment of closure. Ann BiomedEng 1994; 22: 371-380
• 43 Lamson TC, Rosenberg G, Geselowitz DB, Deutsch S, Stinebring DR, Frangos JA, Tarbell JM. Relative blood damage in the three phases of a prosthetic heart valve flow cycle. ASAIO J 1993; 39: M626-M633
• 44 Huang ZJ, Merkle CL, Abdallah S, Tarbell JM. Numerical simulation of unsteady laminar flow through a tilting disk heart valve: prediction of vortex shedding. J Biomech 1994; 27: 391-402
• 45 Berkow RL, Wang D, Larrick JW, Dodson RW, Howard TH. Enhancement of neutrophil superoxide production by preincubation with recombinant human tumor necrosis factor. J Immunol 1987; 139: 3783-3791
• 46 Del MaschioA, Corvazier E, Maillet F, Kazatchkine MD, Maclouf J. Platelet-dependent induction and amplification of polymorphonuclear leukocyte lysosomal enzyme release. Br J Haematol 1989; 72: 329-335