Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1983 Dec;113(3):291–299.

Antiinflammatory effects of endotoxin. Inhibition of rabbit polymorphonuclear leukocyte responses to complement (C5)-derived peptides in vivo and in vitro.

J T Rosenbaum, K T Hartiala, R O Webster, E L Howes Jr, I M Goldstein
PMCID: PMC1916362  PMID: 6228151

Abstract

Although capable of provoking a variety of inflammatory effects, endotoxin (bacterial lipopolysaccharide) paradoxically has been reported to be antiinflammatory. The authors have found that single intravenous injections of Escherichia coli endotoxin, 24 hours before challenge, inhibit almost completely the vascular permeability changes and exudation of polymorphonuclear leukocytes induced in rabbit skin by reversed passive Arthus reactions. Whereas intravenous injections of endotoxin also caused modest inhibition of the vascular permeability changes induced in rabbit skin by the synthetic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP), exudation of polymorphonuclear leukocytes was unaffected. Polymorphonuclear leukocytes from rabbits given single injected doses of endotoxin exhibited markedly diminished chemotactic and degranulation responses to complement (C5)-derived peptides in vitro. Responses of these cells to FMLP, however, were normal. These data suggest that selective suppression of polymorphonuclear leukocyte responses to C5-derived peptides accounts, in part, for the antiinflammatory effects of endotoxin.

Full text

PDF
291

Images in this article

294Figure 1
on p.294
295Figure 2
on p.295

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. Brittinger G., Hirschhorn R., Douglas S. D., Weissmann G. Studies on lysosomes. XI. Characterization of a hydrolase-rich fraction from human lymphocytes. J Cell Biol. 1968 May;37(2):394–411. doi: 10.1083/jcb.37.2.394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cohen A. B., Rossi M., Geczy D., Knight L. Neutrophil turnover in normal rabbit lungs. J Clin Invest. 1982 Apr;69(4):794–798. doi: 10.1172/JCI110518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cousins S. W., Rosenbaum J. T., Guss R. B., Egbert P. R. Ocular albumin fluorophotometric quantitation of endotoxin-induced vascular permeability. Infect Immun. 1982 May;36(2):730–736. doi: 10.1128/iai.36.2.730-736.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Crawford J. P., Movat H. Z., Ranadive N. S., Hay J. B. Pathways to inflammation induced by immune complexes: development of the Arthus reaction. Fed Proc. 1982 Jul;41(9):2583–2587. [PubMed] [Google Scholar]
  6. Dahinden C., Galanos C., Fehr J. Granulocyte activation by endotoxin. I. Correlation between adherence and other granulocyte functions, and role of endotoxin structure on biologic activity. J Immunol. 1983 Feb;130(2):857–862. [PubMed] [Google Scholar]
  7. Donabedian H., Gallin J. I. Deactivation of human neutrophil chemotaxis by chemoattractants: effect on receptors for the chemotactic factor f-Met-Leu-Phe. J Immunol. 1981 Sep;127(3):839–844. [PubMed] [Google Scholar]
  8. GILBERT V. E., BRAUDE A. I. Reduction of serum complement in rabbits after injection of endotoxin. J Exp Med. 1962 Oct 1;116:477–490. doi: 10.1084/jem.116.4.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gallin J. I., Wright D. G., Malech H. L., Davis J. M., Klempner M. S., Kirkpatrick C. H. Disorders of phagocyte chemotaxis. Ann Intern Med. 1980 Apr;92(4):520–538. doi: 10.7326/0003-4819-92-4-520. [DOI] [PubMed] [Google Scholar]
  10. Goetzl E. J., Austen K. F. A neutrophil-immobilizing factor derived from human leukocytes. I. Generation and partial characterization. J Exp Med. 1972 Dec 1;136(6):1564–1580. doi: 10.1084/jem.136.6.1564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Goetzl E. J., Boeynaems J. M., Oates J. A., Hubbard W. C. Stimulus-specificity of the chemotactic deactivation of human neutrophils by lipoxygenase products of arachidonic acid. Prostaglandins. 1981 Aug;22(2):279–288. doi: 10.1016/0090-6980(81)90042-3. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. HUMPHREY J. H. The mechanism of Arthus reactions. I. The role of polymorphonuclear leucocytes and other factors in reversed passive Arthus reactions in rabbits. Br J Exp Pathol. 1955 Jun;36(3):268–282. [PMC free article] [PubMed] [Google Scholar]
  14. Henson P. M., Schwartzman N. A., Zanolari B. Intracellular control of human neutrophil secretion. II. Stimulus specificity of desensitization induced by six different soluble and particulate stimuli. J Immunol. 1981 Aug;127(2):754–759. [PubMed] [Google Scholar]
  15. Henson P. M. The immunologic release of constituents from neutrophil leukocytes. II. Mechanisms of release during phagocytosis, and adherence to nonphagocytosable surfaces. J Immunol. 1971 Dec;107(6):1547–1557. [PubMed] [Google Scholar]
  16. Henson P. M., Zanolari B., Schwartzman N. A., Hong S. R. Intracellular control of human neutrophil secretion. I. C5a-induced stimulus-specific desensitization and the effects of cytochalasin B. J Immunol. 1978 Sep;121(3):851–855. [PubMed] [Google Scholar]
  17. Howes E. L., Jr, McKay D. G. Comparison of the ocular effects of circulating endotoxin and immune complexes: role of vasoactive amines. J Immunol. 1975 Feb;114(2 Pt 2):734–737. [PubMed] [Google Scholar]
  18. Howes E. L., Jr, McKay D. G. Effect of hypovolemic shock on the generalized Shwartzman reaction. Haemostasis. 1977;6(4):244–251. doi: 10.1159/000214186. [DOI] [PubMed] [Google Scholar]
  19. Issekutz A. C., Biggar W. D. Influence of serum-derived chemotactic factors and bacterial products on human neutrophil chemotaxis. Infect Immun. 1977 Jan;15(1):212–220. doi: 10.1128/iai.15.1.212-220.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Johnson K. J., Anderson T. P., Ward P. A. Suppression of immune complex-induced inflammation by the chemotactic factor inactivator. J Clin Invest. 1977 May;59(5):951–958. doi: 10.1172/JCI108717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kimball H. R., Melmon M. L., Wolff S. M. Endotoxin-induced kinin production in man. Proc Soc Exp Biol Med. 1972 Mar;139(3):1078–1082. doi: 10.3181/00379727-139-36302. [DOI] [PubMed] [Google Scholar]
  22. Kunkel S. L., Thrall R. S., Kunkel R. G., McCormick J. R., Ward P. A., Zurier R. B. Suppression of immune complex vasculitis in rats by prostaglandin. J Clin Invest. 1979 Nov;64(5):1525–1529. doi: 10.1172/JCI109611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kurland J. I., Bockman R. Prostaglandin E production by human blood monocytes and mouse peritoneal macrophages. J Exp Med. 1978 Mar 1;147(3):952–957. doi: 10.1084/jem.147.3.952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Latour J. G., McKay D. G. Requirement of the adrenal glands for provocation of the generalized Shwartzman reaction. Lab Invest. 1970 Apr;22(4):281–285. [PubMed] [Google Scholar]
  25. Lynch J. M., Lotner G. Z., Betz S. J., Henson P. M. The release of a platelet-activating factor by stimulated rabbit neutrophils. J Immunol. 1979 Sep;123(3):1219–1226. [PubMed] [Google Scholar]
  26. MEIER R., BEIN H. J., JAQUES R. The action of bacterial polysaccharides on allergic phenomena. Int Arch Allergy Appl Immunol. 1957;11(1-2):101–118. doi: 10.1159/000228406. [DOI] [PubMed] [Google Scholar]
  27. Moeller G. R., Terry L., Snyderman R. The inflammatory response and resistance to endotoxin in mice. J Immunol. 1978 Jan;120(1):116–123. [PubMed] [Google Scholar]
  28. Morrison D. C., Kline L. F. Activation of the classical and properdin pathways of complement by bacterial lipopolysaccharides (LPS). J Immunol. 1977 Jan;118(1):362–368. [PubMed] [Google Scholar]
  29. O'Flaherty J. T., Kreutzer D. L., Showell H. J., Vitkauskas G., Becker E. L., Ward P. A. Selective neutrophil desensitization to chemotactic factors. J Cell Biol. 1979 Mar;80(3):564–572. doi: 10.1083/jcb.80.3.564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Perez H. D., Lipton M., Goldstein I. M. A specific inhibitor of complement (C5)-derived chemotactic activity in serum from patients with systemic lupus erythematosus. J Clin Invest. 1978 Jul;62(1):29–38. doi: 10.1172/JCI109110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. STETSON C. A., Jr Studies on the mechanism of the Shwartzman phenomenon; certain factors involved in the production of the local hemorrhagic necrosis. J Exp Med. 1951 May;93(5):489–504. doi: 10.1084/jem.93.5.489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Shen S. M., Rapaport S. I., Feinstein D. I. Intravascular clotting after endotoxin in rabbits with impaired intrinsic clotting produced by a factor VIII antibody. Blood. 1973 Oct;42(4):523–534. [PubMed] [Google Scholar]
  33. Skubitz K. M., Craddock P. R. Reversal of hemodialysis granulocytopenia and pulmonary leukostasis: A clinical manifestation of selective down-regulation of granulocyte responses to C5adesarg. J Clin Invest. 1981 May;67(5):1383–1391. doi: 10.1172/JCI110166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. ULMER D. D., VALLEE B. L., WACKER W. E. Metalloenzymes and myocardial infarction. II. Malic and lactic dehydrogenase activities and zinc concentrations in serum. N Engl J Med. 1956 Sep 6;255(10):450–456. doi: 10.1056/NEJM195609062551001. [DOI] [PubMed] [Google Scholar]
  35. Verghese M. W., Snyderman R. Differential anti-inflammatory effects of LPS in susceptible and resistant mouse strains. J Immunol. 1981 Jul;127(1):288–293. [PubMed] [Google Scholar]
  36. WOLFF S. M., MULHOLLAND J. H., WARD S. B. QUANTITATIVE ASPECTS OF THE PYROGENIC RESPONSE OF RABBITS TO ENDOTOXIN. J Lab Clin Med. 1965 Feb;65:268–275. [PubMed] [Google Scholar]
  37. Webster R. O., Larsen G. L., Henson P. M. In vivo clearance and tissue distribution of C5a and C5a des arginine complement fragments in rabbits. J Clin Invest. 1982 Dec;70(6):1177–1183. doi: 10.1172/JCI110716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Webster R. O., Larsen G. L., Mitchell B. C., Goins A. J., Henson P. M. Absence of inflammatory lung injury in rabbits challenged intravascularly with complement-derived chemotactic factors. Am Rev Respir Dis. 1982 Mar;125(3):335–340. doi: 10.1164/arrd.1982.125.3.335. [DOI] [PubMed] [Google Scholar]
  39. Wedmore C. V., Williams T. J. Control of vascular permeability by polymorphonuclear leukocytes in inflammation. Nature. 1981 Feb 19;289(5799):646–650. doi: 10.1038/289646a0. [DOI] [PubMed] [Google Scholar]
  40. Zigmond S. H., Hirsch J. G. Leukocyte locomotion and chemotaxis. New methods for evaluation, and demonstration of a cell-derived chemotactic factor. J Exp Med. 1973 Feb 1;137(2):387–410. doi: 10.1084/jem.137.2.387. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES