Abstract
It is well known that xenotransplantation leads to immediate graft dysfunction. This study was designed to specifically examine the role of platelets in mediating lung hyperacute xenorejection (HXR) in a guinea pig-to-rat model. A total of 18 lungs were perfused with blood using an ex vivo apparatus. The animals were divided into the following four groups: a CE group comprising circuit only with rat blood; a SYN group comprising rat lungs and blood; a XE group comprising guinea pig lungs and rat blood; and an SH group comprising guinea pig lungs and rat blood with sarpogrelate hydrochloride, a suppresser of platelet aggregation. The platelet and serotonin in the blood were lower and the wet/dry weight ratio of the lung (W/D) in the XE group were higher than those in the SYN group after perfusion. The platelet count was higher, but the serotonin and W/D were lower in the SH group than in the XE group. These results suggest that platelets strongly affect HXR. Thus, the administration of drugs to suppress platelet aggregation would reduce xenotransplanted lung edema.
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References
Lin SS, Platt JL (1996) Immunologic barriers to xenotransplantation. J Heart Lung Transplant 15:547–555
Egan TM, Cooper JD (1991) The lung following transplantation. In: Crystal RG, West JB, et al. (eds) The lung Raven, New York, pp 2205–2215
Kroshus TJ, Bolman RM III, Dalmasso AP (1996) Selective IgM depletion prolongs organ survival in an ex vivo model of pig-to-human xenotransplantation. Transplantation 62:5–12
Hara H, Osakabe M, Kitajima A, Tamao Y, Kikumoto R, (1991) MCT-9042, a new antiplatelet agent is a selective S2-serotonergic receptor antagonist. Thormb Haemost 65:415–420
Tsuchihashi H, Yagi N, Kimura M, Shirota K, Kitami J, Nagatomo T (1991) Binding characteristics of [3H]ketanserin for serotonin-2 receptor in the rabbit platelet. J Pharmacobiol Dyn 14:461–466
Iuliano L, Colavita AR, Leo R, Pratico D, Violi F (1997) Oxygen free radicals and platelet activation. Free Radic Biol Med 22:999–1006
Colman RB, Habal M, Hollenberg NK, Birtch AG, Busch GJ (1976) Hyperacute renal allograft rejection in the primate: therapeutic limitations of antiplatelet agents alone and combined with heparin. Am J Pathol 82:25–42
Shons AR, Najarian JS (1974) Modification of xenograft rejection by aspirin, dextran, and cinanserin: the importance of platelets in hyperacute rejection. Transplant Proc 6:435–440
Adachi H, Rosengard BR, Hutchins GM, Hall TS, Baumgartner WA, Borkon AM, Reitz BA (1987) Effects of cyclosporine, aspirin, and cobra venom factor on discordant cardiac xenograft survival in rats. Transplant Proc 19:1145–1148
Ito S, Camussi G, Tetta C, Milgrom K, Andres G (1984) Hyperacute renal allograft rejection in the rabbit: the role of plateletactivating factor and of cationic proteins derived from polymorphonuclear leukocytes and from platelets. Lab Invest 51:148–161
Cywes R, Mullen JBM, Stratis MA, Greig PD, Levy GA, Harvey PRC, Strasberg SM (1993) Prediction of the outcome of transplantation in man by platelet adherence in donor liver allografts: evidence of the importance of preservation injury. Transplantation 56:316–323
Bustos M, Platt JL (1997) Platelet-endothelial cell interactions in a xenograft model. Transplant Proc 29:886
Hattori R, Hamilton KK, Fugate RD, McEver RP, Sims PJ (1989) Stimulated secretion of endothelial von Willebrand factor is accompanied by rapid redistribution to the cell surface of the intracellular granule membrane protein GMP-140. J Biol Chem 264:7768–7771
Zehr KJ, Herskowitz A, Lee PC, Kumar P, Gillinov AM, Baumgartner WA (1994) Neutrophil adhesion and complement inhibition prolongs survival of cardiac xenografts in discordant species. Transplantation 57:900–906
Frishman WH, Huberfeld S, Okin S, Wang YH, Kumar A, Shareef B (1995) Serotonin and serotonin antagonism in cardiovascular and noncardiovascular disease. J Clin Pharmacol 35:541–572
Thomas DP, Vane JR (1967) 5-Hydroxytryptamine in the circulation of the dog. Nature 216:335–338
Herve P, Launay JM, Scrobohaci ML, Brenot F, Simonneau G, Petitpretz P, Poubeau P, Cerrina J, Duroux P, Drouet L (1995) Increased plasma serotonin in pulmonary hypertension. Am J Med 99:249–254
Yuan XJ, Bright RT, Aldinger AM, Rubin LJ (1997) Nitric oxide inhibits serotonin-induced calcium release in pulmonary artery smooth muscle cell. Am J Physiol 272 (Lung Cell Mol Physiol 16):L44-L50
Sheldon WS, Crawford MP, Brewer NR (1979) Morphophysiology. In: Baker HJ, Lindsey JR, Weisbroth SH (eds) The laboratory rat. Academic, New York, pp 83–85
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Nonaka, M., Kadokura, M., Kataoka, D. et al. Platelets as participants in hyperacute guinea pig-to-rat lung xenorejection. Surg Today 29, 255–259 (1999). https://doi.org/10.1007/BF02483016
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DOI: https://doi.org/10.1007/BF02483016