Interactions between Neutrophils and Coronary Microvessels

  • F. M. Williams
  • T. J. Williams


In order to maintain its work load, the myocardium receives a relatively high proportion of the cardiac output. Interruption of this blood supply for even short periods of time can result in irreversible injury to the myocytes and the onset of tissue necrosis. If a sufficiently large region of myocardium is affected, this can severely compromise the function of the heart. This sequence of events can be initiated by narrowing of the coronary arteries with atherosclerosis, occlusion of vessels by platelet thrombi and/or coronary artery spasm. In experimental studies this situation can be mimicked by physical occlusion of the artery or generation of a platelet plug, using an intravascular copper coil. Such techniques have been used extensively in experimental studies aimed at gaining a better understanding of the sequence of events following the onset of ischaemia and ultimately in identifying means of protecting myocardial tissue.


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  1. Annable, C. R., McManus, L. M., Carey, K. D. and Pinckard, R. N. (1985). Isolation of platelet-activating factor (PAF) from ischemic baboon myocardium. Fed. Proc., 44, 1271Google Scholar
  2. Arfors, K.-E., Lundberg, C., Lindbom, L., Lundberg, K., Beatty, P. G. and Harlan, J. M. (1987). A monoclonal antibody to the membrane glycoprotein complex CD18 inhibits polymorphonuclear leukocyte accumulation and plasma leakage in vivo. Blood, 69, 338-340PubMedGoogle Scholar
  3. Armiger, L. C. and Gavin, J. B. (1975). Changes in the microvasculature of ischemic and infarcted myocardium. Lab. Invest., 33, 51–56PubMedGoogle Scholar
  4. Arnaout, M. A., Spits, H., Terhorst, C., Pitt, J. and Todd, R. F. (1984). Deficiency of a leukocyte surface glycoprotein (LFA-1) in two patients with Mo 1 deficiency. Effects of cell activation on Mo 1/LFA-1 surface expression in normal and deficient leukocytes. J. Clin. Invest., 74, 1291–1300PubMedPubMedCentralCrossRefGoogle Scholar
  5. Beaubien, B. C., Collins, P. D., Jose, P. J., Totty, N. F., Waterfield, M. D., Hsuan, J. and Williams, T. J. (1990). A novel neutrophil chemoattractant generated during an inflammatory reaction in the rabbit peritoneal cavity in vivo: purification, partial amino acid sequence and structural relationship to interleukin 8. Biochem. J., 271, 797–801PubMedPubMedCentralCrossRefGoogle Scholar
  6. Biesecker, G. (1983). Biology of disease. Membrane attack complex of complement as a pathologic mediator. Lab. Invest., 49, 237–249PubMedGoogle Scholar
  7. Bjork, J., Hedquist, P. and Arfors, K.-E. (1982). Increase in vascular permeability induced by Leukotriene B4 and the role of polymorphonuclear leukocytes. Inflammation, 6, 189–200PubMedCrossRefGoogle Scholar
  8. Chatelain, P., Latour, J.-G., Tran, D., De Lorgeril, D., Dupras, G. and Bourassa, M. (1987). Neutrophil accumulation in experimental myocardial infarcts: relation with extent of injury and effect of reperfusion. Circulation, 75, 1083–1090PubMedCrossRefGoogle Scholar
  9. Colditz, I., Zwahlen, R., Dewald, B. and Baggiolini, M. (1989). In vivo inflammatory activity of neutrophil-activating factor, a novel chemotactic peptide derived from human monocytes. Am. J. Pathol., 134, 755–760PubMedPubMedCentralGoogle Scholar
  10. Collins, P. D., Jose, P. J. and Williams, T. J. (1991). The sequential generation of neutrophil chemoattractant proteins in acute inflammation in the rabbit in vivo: relationship between C5a and a protein with the characteristics of IL-8. J. Immunol., 146, 677–684PubMedGoogle Scholar
  11. Crowley, C. A., Curnutte, J. T., Rosin, R. E., Andre-Schwartz, J., Gallin, J. I., Klempner, M., Snyderman, R., Southwick, F. S., Stossel, T. P. and Babior, B. M. (1980). An inherited abnormality of neutrophil adhesion. Its genetic transmission and its association with missing protein. New Engl. J. Med., 302, 1163–1168PubMedGoogle Scholar
  12. Engler, R. L., Schmid-Schonbein, G. W. and Pavelec, R. S. (1983). Leukocyte capillary plugging in myocardial ischemia and reperfusion in the dog. Am. J. Pathol., 111, 98–111PubMedPubMedCentralGoogle Scholar
  13. Engler, R. L., Dahlgren, M. D., Peterson, M. A., Dobbs, A. and Schmid-Schonbein, G. W. (1986). Accumulation of polymorphonuclear leucocytes during 3-h experimental myocardial ischemia. Am. J. Physiol., 251, H93–H101PubMedGoogle Scholar
  14. Fishbein, M. C., Maclean, D. and Maroko, P. R. (1978). The histopathologic evolution of myocardial infarction. Chest., 73, 843–849PubMedCrossRefGoogle Scholar
  15. Giclas, P. C., Pinckard, R. N. and Olson, M. S. (1979). In vitro activation of complement by isolated human heart subcellular membranes. J. Immunol., 122, 146–151PubMedGoogle Scholar
  16. Harlan, J. M., Killen, P. D., Senecal, F., Schwartz, B. R., Yee, E. K., Taylor, R. F., Beatty, P. G., Price, T. and Ochs, H. D. (1985). The role of neutrophil membrane glycoprotein GP-150 in neutrophil adherence to endothelium in vitro. Blood, 66, 167–178PubMedGoogle Scholar
  17. Hernandez, L. A., Grisham, M. B., Twohig, B., Arfors, K. E., Harlan, J. M. and Granger, D. N. (1987). Role of neutrophils in ischemia-reperfusion-induced microvascular injury. Am. J. Pathol., 253, 699–703Google Scholar
  18. ISIS-2 Collaborative Group (1988). Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17 187 cases of suspected acute myocardial infarction: ISIS-2. Lancet, ii, 349–361Google Scholar
  19. Jolly, S. R., Kane, W. J., Hook, B. G., Abrams, G. D., Kunkel, S. L. and Lucchesi, B. R. (1986). Reduction of myocardial infarct size by neutrophil depletion: Effect of duration of occlusion. Am. Heart J., 112, 682–690PubMedCrossRefGoogle Scholar
  20. Kloner, R. A., Ganote, C. E. and Jennings, R. B. (1974). The ‘no-reflow’ phenomenon after temporary coronary occlusion in the dog. J. Clin. Invest., 54, 1496–1508PubMedPubMedCentralCrossRefGoogle Scholar
  21. Langlois, P. F. and Gawryl, M. S. (1988). Detection of the terminal complement complex in patient plasma following acute myocardial infarction. Atherosclerosis, 70, 95–105PubMedCrossRefGoogle Scholar
  22. Maclean, D., Fishbein, M. C., Braunwald, E. and Maroko, P. R. (1978). Long-term preservation of ischemic myocardium after experimental coronary artery occlusion. J. Clin. Invest., 61, 541–551PubMedPubMedCentralCrossRefGoogle Scholar
  23. McManus, L. M., Kolb, W. P., Crawford, M. H., O'Rourke, R. A., Grover, F. L. and Pinckard, R. N. (1983). Complement localization in ischemic baboon myocardium. Lab. Invest., 48, 436–447PubMedGoogle Scholar
  24. Majno, G., Schoefl, G. I. and Palade, G. (1961). Studies on inflammation. The site of action of histamine and serotonin on the vascular tree; a topographic study. J. Cell Biol., 11, 607–626CrossRefGoogle Scholar
  25. Mallory, G. K., White, P. D. and Salcedo-Salgar, J. (1939). The speed of healing of myocardial infarction. A study of the pathologic anatomy in seventy-two cases. Am. Heart J., 18, 647–671Google Scholar
  26. Maroko, P. R., Carpenter, C. B., Chiariello, M., Fishbein, M. C., Radvany, P., Knostman, J. D. and Hale, S. L. (1978). Reduction by cobra venom factor of myocardial necrosis after coronary artery occlusion. J. Clin. Invest., 61, 661–670PubMedPubMedCentralCrossRefGoogle Scholar
  27. Mullane, K., Hatala, M. A., Kraemer, R., Sessa, W. and Westlin, W. (1987). Myocardial salvage induced by REV-5901: An inhibitor and antagonist of the leukotrienes. J. Cardiovasc. Pharmacol., 10, 398–406PubMedCrossRefGoogle Scholar
  28. Mullane, K. M., Read, N., Salmon, J. A. and Moncada, S. (1984). Role of leukocytes in acute myocardial infarction in anaesthetized dogs: relationship to myocardial salvage by anti-inflammatory drugs. J. Pharmacol. Exp. Ther., 228, 510–522PubMedGoogle Scholar
  29. Nagai, K. and Katori, M. (1988). Possible changes in the leukocyte membrane as a mechanism of leukocyte adhesion to the venular walls induced by leukotriene B4 and fMLP in the microvasculature of the hamster cheek pouch. Int. J. Microcirc., 7, 305–314Google Scholar
  30. Nourshargh, S., Rampart, M., Hellewell, P. G., Jose, P. J., Harlan, J. M., Edwards, A. J. and Williams, T. J. (1989). Accumulation of 111In-neutrophils in rabbit skin in allergic and non-allergic inflammatory reactions in vivo: inhibition by neutrophil pretreatment in vitro with a monoclonal antibody recognising the CD18 antigen. J. Immunol., 142, 3193–3198PubMedGoogle Scholar
  31. Nourshargh, S. and Williams, T. J. (1990). Evidence that a receptor operated event on the neutrophil mediates neutrophil accumulation in vivo: pretreatment of "'In-neutrophils with pertussis toxin in vitro inhibits their accumulation in vivo. J. Immunol., 145, 2633–2638PubMedGoogle Scholar
  32. Reimer, K. A., Jennings, R. B., Cobb, F. R., Murdock, R. H., Greenfield, J. C., Becker, L. C., Bulkley, B. R., Hutchins, G. M., Schwartz, R. P., Bailey, K. R. and Passamani, E. R. (1985). Animal models for protecting ischemic myocardium: results of the NHLBI cooperative study. Comparison of unconscious and conscious dog models. Circ. Res., 56, 651–665PubMedCrossRefGoogle Scholar
  33. Reimer, K. A., Murry, C. E. and Richard, V. J. (1989). The role of neutrophils and free radicals in the ischemic-reperfused heart: Why the confusion and controversy? J. Mol. Cell. Cardiol., 21, 1225–1239PubMedCrossRefGoogle Scholar
  34. Romson, J. L., Hook, B. G., Kunkel, S. L., Abrams, G. D., Schork, M. A. and Lucchesi, B. R. (1983). Reduction of the extent of ischemic myocardial injury by neutrophil depletion in the dog. Circulation, 67, 1016–1023PubMedCrossRefGoogle Scholar
  35. Romson, J. L., Hook, B. G., Rigot, V. H., Schork, M. A., Swanson, D. P. and Lucchesi, B. R. (1982). The effect of ibuprofen on accumulation of indium-111-labelled platelets and leukocytes in experimental myocardial infarction. Circulation, 66, 1002–1011PubMedCrossRefGoogle Scholar
  36. Sasaki, K., Ueno, A., Katori, M. and Kikawada, R. (1988). Detection of leukotriene B4 in cardiac tissue and its role in infarct extension through leucocyte migration. Cardiovasc. Res., XXII, 142–148Google Scholar
  37. Schafer, H., Mathey, D., Hugo, F. and Bhakdi, S. (1986). Deposition of the terminal C5b-9 complement complex in infarcted areas of human myocardium. J. Immunol., 137, 1945–1949PubMedGoogle Scholar
  38. Seewaldt-Becker, E., Rothlein, R. and Dammgen, J. W. (1990). CDw18 dependent adhesion of leukocytes to endothelium and its relevance for cardiac reperfusion. In Springer, T. A., Anderson, D. C., Rosenthal, A. S. and Rothlein, R. (Eds), Leukocyte Adhesion Molecules. Springer, New York, pp. 138–148CrossRefGoogle Scholar
  39. Seifert, P. S., Hugo, F., Hansson, G. K. and Bhakdi, S. (1989). Prelesional complement activation in experimental atherosclerosis. Terminal C5b-9 complement deposition coincides with cholesterol accumulation in the aortic intima of hypercholesterolemic rabbits. Lab. Invest., 60, 747–754PubMedGoogle Scholar
  40. Simpson, P. J., Mitsos, S. E., Ventura, A., Gallagher, K. P., Fantone, J. C., Abrams, G. D., Schork, M. A. and Lucchesi, B. R. (1987). Prostacyclin protects ischemic reperfused myocardium in the dog by inhibition of neutrophil activation. Am. Heart J., 113, 129–137PubMedCrossRefGoogle Scholar
  41. Simpson, P. J., Todd, R. F. III, Fantone, J. C., Mickelson, J. K., Griffin, J. D. and Lucchesi, B. R. (1988). Reduction of experimental canine myocardial reperfusion injury by a monoclonal antibody (Anti-Mol, Anti-CD11b) that inhibits leukocyte adhesion. J. Clin. Invest., 81, 624–629PubMedPubMedCentralCrossRefGoogle Scholar
  42. Smith, J. K., Grisham, M. B., Granger, D. N. and Korthuis, R. J. (1989). Free radical defense mechanisms and neutrophil infiltration in postischemic skeletal muscle. Am. Physiol. Soc., 256, H789–H793Google Scholar
  43. Snyderman, R., Phillips, J. and Mergenhagen, S. E. (1970). Polymorphonuclear leukocyte chemotactic activity in rabbit serum and guinea pig serum treated with immune complexes: evidence for C5a as the major chemotactic factor. Infect. Immun., 1, 521–525PubMedPubMedCentralGoogle Scholar
  44. Sommers, H. M. and Jennings, R. B. (1964). Experimental acute myocardial infarction. Histologic and histochemical studies of early myocardial infarcts induced by temporary or permanent occlusion of a coronary artery. Lab. Invest., 13, 1491–1503PubMedGoogle Scholar
  45. Stahl, G. L., Terashita, Z.-I. and Lefer, A. M. (1988). Role of platelet activating factor in propagation of cardiac damage during myocardial ischemia. J. Pharmacol. Exp. Ther., 244, 898–904PubMedGoogle Scholar
  46. Tillmanns, H. and Kubler, W. (1984). What happens in the microcirculation. In Hearse, D. J. and Yellon, D. M. (Eds), Therapeutic Approaches to Myocardial Infarct Size Limitation. Raven Press, New York, pp. 107–124Google Scholar
  47. Van de Werf, F. and Arnold, A. E. R. (1988). Intravenous tissue plasminogen activator and size of infarct, left ventricular function, and survival in acute myocardial infarction. Br. Med. J., 297, 1374–1379CrossRefGoogle Scholar
  48. Wedmore, C. V. and Williams, T. J. (1981). Control of vascular permeability by polymorpho-nuclear leukocytes in inflammation. Nature, 289, 646–650PubMedCrossRefGoogle Scholar
  49. Weisman, H. F., Bartow, T., Leppo, M. K., Marsh, H. C., Carson, G. R. Concino, M. F., Boyle, M. P., Roux, K. H., Weisfeldt, M. L. and Fearon, D. T. (1990). Soluble human complement receptor type 1: in vivo inhibitor of complement suppressing post-ischemic myocardial inflammation and necrosis. Science, 249, 146–151PubMedCrossRefGoogle Scholar
  50. Williams, F. M., Collins, P. D., Tanniere-Zeller, M. and Williams, T. J. (1990). The relationship between neutrophils and increased microvascular permeability in a model of myocardial ischaemia and reperfusion in the rabbit. Br. J. Pharmacol., 100, 729–734PubMedPubMedCentralCrossRefGoogle Scholar

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© Macmillan Publishers Limited 1992

Authors and Affiliations

  • F. M. Williams
  • T. J. Williams

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