Platelet-endothelial cell interaction in pulmonary microcirculation: the role of PARS

Summary

Accumulation of platelets might contribute to acute lung injury during systemic inflammation. The aim of the study was to elucidate the role of the poly (ADP-ribose) synthetase, a nucleotide-polymerizising enzyme, in mediation of platelet-endothelial cell interaction through regulation of adhesion molecules within the pulmonary microcirculation during endotoxemia. We used in vivo fluorescence microscopy to quantify kinetics of fluorescently labeled erythrocytes and platelets in rabbit pulmonary arterioles and venules. Six hours after onset of endotoxin infusion we observed a massive interaction of platelets with the microvascular endothelial cells, whereas under control conditions, no platelet sequestration was measured. An up-regulation of P- and E-selectin was detected in lung tissue following endotoxin infusion by immunohistochemistry and Western blot analysis. Blockade of endothelial P-selectin with fucoidin resulted in a reduction of the endotoxin-induced platelet-endothelial cell interaction. Inhibition of poly (ADP-ribose) synthetase by 3-aminobenzamide inhibited the endotoxin-induced expression of endothelial P- and E-selectin and the subsequent recruitment of platelets. In summary, we provide first in vivo evidence that platelets accumulate in pulmonary microcirculation following endotoxemia. Poly (ADP-ribose) synthetase seems to mediate this platelet-endothelial cell interaction via P- and E-selectin expressed on the surface of microvascular endothelium.

Keywords

Acute lung injury - poly (ADP-ribose) synthetase (PARS) - in vivo fluorescence intravital microscopy - thrombocytes - P- and E-selectin

• References

• 1 Heffner JE, Sahn SA, Repine JE. The role of platelets in the adult respiratory distress syndrome. Culprits or bystanders?. Am Rev Respir Dis 1987; 135: 482-92.
• 2 Okada Y, Marchevsky AM, Zuo XJ. et al. Accumulation of platelets in rat syngeneic lung transplants: a potential factor responsible for preservation-reperfusion injury. Transplantation 1997; 64: 801-6.
• 3 Barry BE, Crapo JD. Patterns of accumulation of platelets and neutrophils in rat lungs during exposure to 100% and 85% oxygen. Am Rev Respir Dis 1985; 132: 548-55.
• 4 Leo R, Pratico D, Iuliano L. et al. Platelet activation by superoxide anion and hydroxyl radicals intrinsically generated by platelets that had undergone anoxia and then reoxygenated. Circulation 1997; 95: 885-91.
• 5 Forde RC, Fitzgerald DJ. Reactive oxygen species and platelet activation in reperfusion injury. Circulation 1997; 95: 787-9.
• 6 Piccardoni P, Evangelista V, Piccoli A. et al. Thrombin-activated human platelets release two NAP-2 variants that stimulate polymorphonuclear leukocytes. Thromb Haemost 1996; 76: 780-5.
• 7 Deuel TF, Senior RM, Chang D. et al. Platelet factor 4 is chemotactic for neutrophils and monocytes. Proc Natl Acad Sci U S A 1981; 78: 4584-7.
• 8 Ruf A, Patscheke H. Platelet-induced neutrophil activation: platelet-expressed fibrinogen induces the oxidative burst in neutrophils by an interaction with CD11C/CD18. Br J Haematol 1995; 90: 791-6.
• 9 Doerschuk CM, Allard MF, Hogg JC. Neutrophil kinetics in rabbits during infusion of zymosan- activated plasma. J Appl Physiol 1989; 67: 88-95.
• 10 Szabo C. The pathophysiological role of peroxynitrite in shock, inflammation, and ischemia-reperfusion injury. Shock 1996; 06: 79-88.
• 11 Cochrane CG. Mechanisms of oxidant injury of cells. Mol Aspects Med 1991; 12: 137-47.
• 12 Schraufstatter I, Hyslop PA, Jackson JH. et al. Oxidant-induced DNA damage of target cells. J Clin Invest 1988; 82: 1040-1050.
• 13 Schraufstatter IU, Hinshaw DB, Hyslop PA. et al. Oxidant injury of cells. DNA strand-breaks activate polyadenosine diphosphate-ribose polymerase and lead to depletion of nicotinamide adenine dinucleotide. J Clin Invest 1986; 77: 1312-1320.
• 14 Szabo C, Zingarelli B, O’Connor M. et al. DNA strand breakage, activation of poly (ADP-ribose) synthetase, and cellular energy depletion are involved in the cytotoxicity of macrophages and smooth muscle cells exposed to peroxynitrite. Proc Natl Acad Sci USA 1996; 93: 1753-8.
• 15 Zingarelli B, O’Connor M, Wong H. et al. Peroxynitrite-mediated DNA strand breakage activates poly-adenosine diphosphate ribosyl synthetase and causes cellular energy depletion in macrophages stimulated with bacterial lipopolysaccharide. J Immunol 1996; 156: 350-8.
• 16 Body SC. Platelet activation and interactions with the microvasculature. J Cardiovasc Pharmacol 1996; 27 Suppl 1: S13-S25.
• 17 Williams MJ, Du X, Loftus JC. et al. Platelet adhesion receptors. Semin Cell Biol 1995; 06: 305-14.
• 18 Massberg S, Enders G, Leiderer R. et al. Platelet-endothelial cell interactions during ischemia/reperfusion: The role of P-selectin. Blood 1998; 92: 507-15.
• 19 Wang ZQ, Auer B, Stingl L. et al. Mice lacking ADPRT and poly(ADP-ribosyl)ation develop normally but are susceptible to skin disease. Genes Dev 1995; 09: 509-20.
• 20 Kuhnle GEH, Kuebler WM, Groh J. et al. Effect of blood flow on the leukocyte-endothelium interaction in pulmonary microvessels. Am J Resp Crit Care Med 1995; 152: 1221-1228.
• 21 Kiefmann R, Heckel K, Dorger M. et al. Role of poly (ADP-ribose) synthetase in pulmonary leukocyte recruitment. Am J Physiol Lung Cell Mol Physiol 2003; 85: L996-L1005.
• 22 Kuebler WM, Kuhnle GEH, Groh J. et al. Leukocyte kinetics in the pulmonary microcirculation: an intravital fluorescence microscopic study. J Appl Physiol 1994; 76: 65-71.
• 23 Kuebler WM, Borges J, Sckell A. et al. Role of L-selectin in leukocyte sequestration in lung capillaries in a rabbit model of endotoxemia. Am J Respir Crit Care Med 2000; 161: 36-43.
• 24 Kuhnle GH, Kiefmann R, Sckell A. et al. Leukocyte sequestration in pulmonary microvessels and lung injury following systemic complement activation in rabbits. J Vasc Res 1999; 36: 289-98.
• 25 Eichhorn ME, Ney L, Massberg S. et al. Platelet kinetics in the pulmonary microcirculation in vivo assessed by intravital microscopy. J Vasc Res 2002; 39: 330-9.
• 26 Massaguer A, Engel P, Perez-del-Pulgar S. et al. Production and characterization of monoclonal antibodies against conserved epitopes of P-selectin (CD62P). Tissue Antigens 2000; 56: 117-28.
• 27 Deryckere F, Gannon F. A one-hour minipreparation technique for extraction of DNA-binding proteins from animal tissues. Biotechniques 1994; 16: 405.
• 28 Dorger M, Jesch NK, Rieder G. et al. Species differences in NO formation by rat and hamster alveolar macrophages in vitro. Am J Respir Cell Mol Biol 1997; 16: 413-20.
• 29 Banasik M, Komura H, Shimoyama M. et al. Specific inhibitors of poly(ADP-ribose) synthetase and mono(ADP-ribosyl)transferase. J Biol Chem 1992; 267: 1569-75.
• 30 Szabo C, Lim LH, Cuzzocrea S. et al. Inhibition of poly (ADP-ribose) synthetase attenuates neutrophil recruitment and exerts antiinflammatory effects. J Exp Med 1997; 186: 1041-9.
• 31 Thiemermann C, Bowes J, Myint FP. et al. Inhibition of the activity of poly(ADP ribose) synthetase reduces ischemia-reperfusion injury in the heart and skeletal muscle. Proc Natl Acad Sci U S A 1997; 94: 679-83.
• 32 Doerschuk CM, Downey GP, Doherty DE. et al. Leukocyte and platelet margination within microvasculature of rabbit lungs. J Appl Physiol 1990; 68: 1956-61.
• 33 Hassa PO, Covic M, Hasan S. et al. The enzymatic and DNA binding activity of PARP-1 are not required for NF-kappa B coactivator function. J Biol Chem 2001; 276: 45588-97.
• 34 Shall S, de Murcia G. Poly(ADP-ribose) polymerase-1: what have we learned from the deficient mouse model?. Mutat Res 2000; 460: 1-15.
• 35 Virag L, Szabo C. The therapeutic potential of poly(ADP-ribose) polymerase inhibitors. Pharmacol Rev 2002; 54: 375-429.
• 36 Mota-Filipe H, Sepodes B, McDonald MC. et al. The novel PARP inhibitor 5-aminoisoquinolinone reduces the liver injury caused by ischemia and reperfusion in the rat. Med Sci Monit 2002; 08: BR444-BR453.
• 37 Veres B, Gallyas F, Varbiro G. et al. Decrease of the inflammatory response and induction of the Akt/protein kinase B pathway by poly- (ADP-ribose) polymerase 1 inhibitor in endotoxin-induced septic shock. Biochem Pharmacol 2003; 65: 1373-82.
• 38 McDonald MC, Mota-Filipe H, Wright JA. et al. Effects of 5-aminoisoquinolinone, a water-soluble, potent inhibitor of the activity of poly (ADP-ribose) polymerase on the organ injury and dysfunction caused by haemorrhagic shock. Br J Pharmacol 2000; 130: 843-50.
• 39 Sikora L, Rao SP, Sriramarao P. Selectindependent rolling and adhesion of leukocytes in nicotine-exposed microvessels of lung allografts. Am J Physiol Lung Cell Mol Physiol 2003; 285: L654-L663.
• 40 Sikora L, Johansson AC, Rao SP. et al. A murine model to study leukocyte rolling and intravascular trafficking in lung microvessels. Am J Pathol 2003; 162: 2019-28.
• 41 Khandoga A, Biberthaler P, Messmer K. et al. Platelet-endothelial cell interactions during hepatic ischemia-reperfusion in vivo: a systematic analysis. Microvasc Res 2003; 65: 71-77.
• 42 Frenette PS, Moyna C, Hartwell DW. et al. Platelet-endothelial interactions in inflamed mesenteric venules. Blood 1998; 91: 1318-24.
• 43 Handa K, Nudelman ED, Stroud MR. et al. Selectin GMP-140 (CD62; PADGEM) binds to sialosyl-Le(a) and sialosyl-Le(x), and sulfated glycans modulate this binding. Biochem Biophys Res Commun 1991; 181: 1223-30.
• 44 Ley K, Linnemann G, Meinen M. et al. Fucoidin, but not yeast polyphosphomannan PPME, inhibits leukocyte rolling in venules of the rat mesentery. Blood 1993; 81: 177-85.
• 45 Kubes P, Jutila M, Payne D. Therapeutic potential of inhibiting leukocyte rolling in ischemia/reperfusion. J Clin Invest 1995; 95: 2510-9.
• 46 Kuebler WM, Kuhnle GE, Groh J. et al. Contribution of selectins to leucocyte sequestration in pulmonary microvessels by intravital microscopy in rabbits. J Physiol 1997; 501: 375-86.
• 47 Szabo C, Cuzzocrea S, Zingarelli B. et al. Endothelial dysfunction in a rat model of endotoxic shock. Importance of the activation of poly (ADP-ribose) synthetase by peroxynitrite. J Clin Invest 1997; 100: 723-35.
• 48 Zhang J, Dawson VL, Dawson TM. et al. Nitric oxide activation of poly(ADP-ribose) synthetase in neurotoxicity. Science 1994; 263: 687-9.
• 49 Zingarelli B, Salzman AL, Szabo C. Genetic disruption of poly (ADP-ribose) synthetase inhibits the expression of P-selectin and intercellular adhesion molecule-1 in myocardial ischemia/reperfusion injury. Circ Res 1998; 83: 85-94.
• 50 Zingarelli B, Szabo C, Salzman AL. Blockade of Poly(ADP-ribose) synthetase inhibits neutrophil recruitment, oxidant generation, and mucosal injury in murine colitis. Gastroenterology 1999; 116: 335-45.