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. 1980 Sep;41(3):512–520.

Enhanced vascular permeability and haemorrhage-inducing activity of rabbit C5ades arg: probable role of polymorphonuclear leucocyte lysosomes.

A C Issekutz, K W Movat, H Z Movat
PMCID: PMC1537049  PMID: 7438564

Abstract

We previously reported that the injection into rabbit skin of rabbit zymosan-activated plasma (ZAP) induces marked polymorphonuclear leucocyte (PMN) infiltration, a transient increase in vascular permeability (1 hr) and prolonged red blood cells extravasation lasting at least 10 hr. Here we describe the fractionation of ZAP to identify the factor(s) responsible for these effects. On CM Sephadex G-25 chromatography, the majority of the leucocyte-attracting, permeability-enhancing and haemorrhage-inducing activities eluted in the high-salt fractions (0 . 6 M ammonium formate, 1 M NaCl pH 5 . 0), suggesting that this is a very basic molecule(s). Furthermore, the three activities eluted in the same fraction on Sephadex G-100, with an apparent molecular weight of 14,000--17,000 daltons. These observations, and the previously described requirement for C5 in the plasma, suggest that C5ades arg is the active factor. Experiments performed in neutropenic rabbits indicated that PMN are required for both the increase in permeability and red cell extravasation. Ultrastructural studies showed extensive degenerative changes in the infiltrating PMNs evident even in 1--2-hr lesions. These ranged from 'watery' cytoplasm, loss of glycogen and cell membrane to segregation and extensive extracellular release of lysosomes. It is postulated that C5ades arg-induced chemotaxis and metabolic perturbations contribute to this rapid degeneration of the PMNs, and that the release of lysosomes from these cells results in progressive vascular injury.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Becker E. L., Showell H. J., Henson P. M., Hsu L. S. The ability of chemotactic factors to induce lysosomal enzyme release. I. The characteristics of the release, the importance of surfaces and the relation of enzyme release to chemotactic responsiveness. J Immunol. 1974 Jun;112(6):2047–2054. [PubMed] [Google Scholar]
  2. Damerau B., Höllerhage H. G., Vogt W. Effects of the cleavage peptides, C3q and C3ai, from the third component of hog complement on leukocyte accumulation and vascular permeability in vivo. Naunyn Schmiedebergs Arch Pharmacol. 1978 Mar;302(1):45–50. doi: 10.1007/BF00586595. [DOI] [PubMed] [Google Scholar]
  3. Desai U., Kreutzer D. L., Showell H., Arroyave C. V., Ward P. A. Acute inflammatory pulmonary reactions induced by chemotactic factors. Am J Pathol. 1979 Jul;96(1):71–83. [PMC free article] [PubMed] [Google Scholar]
  4. Fernandez H. N., Hugli T. E. Partial characterization of human C5a anaphylatoxin. I. Chemical description of the carbohydrate and polypeptide prtions of human C5a. J Immunol. 1976 Nov;117(5 Pt 1):1688–1694. [PubMed] [Google Scholar]
  5. Fernandez H. N., Hugli T. E. Primary structural analysis of the polypeptide portion of human C5a anaphylatoxin. Polypeptide sequence determination and assignment of the oligosaccharide attachment site in C5a. J Biol Chem. 1978 Oct 10;253(19):6955–6964. [PubMed] [Google Scholar]
  6. Goldstein I., Hoffstein S., Gallin J., Weissmann G. Mechanisms of lysosomal enzyme release from human leukocytes: microtubule assembly and membrane fusion induced by a component of complement. Proc Natl Acad Sci U S A. 1973 Oct;70(10):2916–2920. doi: 10.1073/pnas.70.10.2916. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hayashi H., Yoshinaga M., Yamamoto S. The nature of a mediator of leucocyte chemotaxis in inflammation. Antibiot Chemother (1971) 1974;19:296–332. doi: 10.1159/000395437. [DOI] [PubMed] [Google Scholar]
  8. Hugli T. E., Müller-Eberhard H. J. Anaphylatoxins: C3a and C5a. Adv Immunol. 1978;26:1–53. doi: 10.1016/s0065-2776(08)60228-x. [DOI] [PubMed] [Google Scholar]
  9. Issekutz A. C., Movat H. Z. The in vivo quantitation and kinetics of rabbit neutrophil leukocyte accumulation in the skin in response to chemotactic agents and Escherichia coli. Lab Invest. 1980 Mar;42(3):310–317. [PubMed] [Google Scholar]
  10. Issekutz A. C., Movat K. W., Movat H. Z. Enhanced vascular permeability and haemorrhage-inducing activity of zymosan-activated plasma. Clin Exp Immunol. 1980 Sep;41(3):505–511. [PMC free article] [PubMed] [Google Scholar]
  11. Kopaniak M. M., Issekutz A. C., Burrowes C. E., Movat H. Z. The quantitation of hemorrhage in the skin. Measurement of hemorrhage in the microcirculation in inflammatory lesions and related phenomena. Proc Soc Exp Biol Med. 1980 Jan;163(1):126–131. doi: 10.3181/00379727-163-40733. [DOI] [PubMed] [Google Scholar]
  12. Kreutzer D. L., Desai U., Orr W., Showell H., Ward P. A. Induction of acute inflammatory reactions in lung following intrapulmonary instillation of preformed chemotactic peptides and purified complement components. Chest. 1979 Feb;75(2 Suppl):259–262. doi: 10.1378/chest.75.2_supplement.259. [DOI] [PubMed] [Google Scholar]
  13. Movat H. Z., Macmorine D. R., Takeuchi Y. The role of PMN-leukocyte lysosomes in tissue injury, inflammation and hypersensitivity. 8. Mode of action and properties of vascular permeability factors released by PMN-leukocytes during 'in vitro' phagocytosis. Int Arch Allergy Appl Immunol. 1971;40(2):218–235. doi: 10.1159/000230407. [DOI] [PubMed] [Google Scholar]
  14. Movat H. Z., Weiser W. J., Glynn M. F., Mustard J. F. Platelet phagocytosis and aggregation. J Cell Biol. 1965 Dec;27(3):531–543. doi: 10.1083/jcb.27.3.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ranadive N. S., Cochrane C. G. Isolation and characterization of permeability factors from rabbit neutrophils. J Exp Med. 1968 Oct 1;128(4):605–622. doi: 10.1084/jem.128.4.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Sacks T., Moldow C. F., Craddock P. R., Bowers T. K., Jacob H. S. Oxygen radicals mediate endothelial cell damage by complement-stimulated granulocytes. An in vitro model of immune vascular damage. J Clin Invest. 1978 May;61(5):1161–1167. doi: 10.1172/JCI109031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Snyderman R., Phillips J., Mergenhagen S. E. 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. 1970 Jun;1(6):521–525. doi: 10.1128/iai.1.6.521-525.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Udaka K., Takeuchi Y., Movat H. Z. Simple method for quantitation of enhanced vascular permeability. Proc Soc Exp Biol Med. 1970 Apr;133(4):1384–1387. doi: 10.3181/00379727-133-34695. [DOI] [PubMed] [Google Scholar]
  19. Vogt W. Activation, activities and pharmacologically active products of complement. Pharmacol Rev. 1974 Jun;26(2):125–169. [PubMed] [Google Scholar]
  20. Wilkinson P. C., McKay I. C. Recognition in leucocyte chemotaxis. Studies with structurally modified proteins. Antibiot Chemother (1971) 1974;19:421–441. [PubMed] [Google Scholar]

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