Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1964 Jul 1;120(1):57–82. doi: 10.1084/jem.120.1.57

PATHOGENESIS OF INFLAMMATION

I. THE PRODUCTION OF AN INFLAMMATORY SUBSTANCE FROM RABBIT GRANULOCYTES IN VITRO AND ITS RELATIONSHIP TO LEUCOCYTE PYROGEN

John M Moses 1, Robert H Ebert 1, Richard C Graham 1, Katherine L Brine 1
PMCID: PMC2137718  PMID: 14194393

Abstract

Material obtained from the in vitro incubation of granulocytes from saline-induced peritoneal exudates of rabbits has been shown to produce inflammation and fever in rabbits. The supernatant material from cells incubated in saline has been termed granulocytic substance (GS) and is heat-labile. Its production is temperature dependent, occurring at 37°C but not at 4°C, requires viable cells, and is inhibited by potassium ions. A similar material is liberated when cells are incubated in a more physiologic medium. Freezing and thawing of granulocytes does not release GS and the active principle cannot be obtained from the incubation of lymphocytes. GS produces a delayed inflammatory response as measured by leucocyte sticking and emigration in the rabbit ear chamber and the leakage of protein-conjugated dye at the site of intradermal injection. The former response can be accurately quantitated by calculation of the inflammatory index from reactions observed in the ear chamber. The inflammatory reaction and the properties of GS distinguish it from a variety of previously described mediators of inflammation, but GS appears to be identical with leucocytic pyrogen. The possible role of GS in delayed and protracted inflammation and its relationship to the pathogenesis of fever are discussed.

Full Text

The Full Text of this article is available as a PDF (1.9 MB).

Selected References

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

  1. AHERN J. J., BARCLAY W. R., EBERT R. H. Modifications of the rabbit ear chamber technique. Science. 1949 Dec 16;110(2868):665–665. doi: 10.1126/science.110.2868.665. [DOI] [PubMed] [Google Scholar]
  2. ALLISON F., Jr, SMITH M. R., WOOD W. B., Jr Studies on the pathogenesis of acute inflammation. I. The inflammatory reaction to thermal injury as observed in the rabbit ear chamber. J Exp Med. 1955 Dec 1;102(6):655–668. doi: 10.1084/jem.102.6.655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. ATKINS E. Pathogenesis of fever. Physiol Rev. 1960 Jul;40:580–646. doi: 10.1152/physrev.1960.40.3.580. [DOI] [PubMed] [Google Scholar]
  4. BENNETT I. L., Jr, BEESON P. B. Studies on the pathogenesis of fever. II. Characterization of fever-producing substances from polymorphonuclear leukocytes and from the fluid of sterile exudates. J Exp Med. 1953 Nov;98(5):493–508. doi: 10.1084/jem.98.5.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. BENNETT I. L., Jr, BEESON P. B. The properties and biologic effects of bacterial pyrogens. Medicine (Baltimore) 1950 Dec;29(4):365–400. doi: 10.1097/00005792-195012000-00003. [DOI] [PubMed] [Google Scholar]
  6. BERLIN R. D., WOOD W. B., Jr Molecular mechanisms involved in the release of pyrogen from polymorphonuclear leucocytes. Trans Assoc Am Physicians. 1962;75:190–197. [PubMed] [Google Scholar]
  7. BHOOLA K. D., CALLE J. D., SCHACHTER M. The effect of bradykinin, serum kallikrein and other endogenous substances on capillary permeability inthe guinea-pig. J Physiol. 1960 Jun;152:75–86. doi: 10.1113/jphysiol.1960.sp006470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. BORNSTEIN D. L., BREDENBERG C., WOOD W. B., Jr Studies on the pathogenesis of fever. XI. Quantitative features of the febrile response to leucocytic pyrogen. J Exp Med. 1963 Mar 1;117:349–364. doi: 10.1084/jem.117.3.349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Beeson P. B., Technical Assistance of Elizabeth Roberts TOLERANCE TO BACTERIAL PYROGENS : I. FACTORS INFLUENCING ITS DEVELOPMENT. J Exp Med. 1947 Jun 30;86(1):29–38. doi: 10.1084/jem.86.1.29. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. COCHRANE C. G., WEIGLE W. O., DIXON F. J. The role of polymorphonuclear leukocytes in the initiation and cessation of the Arthus vasculitis. J Exp Med. 1959 Sep 1;110:481–494. doi: 10.1084/jem.110.3.481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. COHN Z. A., HIRSCH J. G. The isolation and properties of the specific cytoplasmic granules of rabbit polymorphonuclear leucocytes. J Exp Med. 1960 Dec 1;112:983–1004. doi: 10.1084/jem.112.6.983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. COLLINS R. D., WOOD W. B., Jr Studies on the pathogenesis of fever. VI. The interaction of leucocytes and endotoxin in vitro. J Exp Med. 1959 Dec 1;110:1005–1016. doi: 10.1084/jem.110.6.1005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ebert R. H., Koch-Weser D. In Vivo Observations of the Shwartzman Phenomenon. Trans Am Clin Climatol Assoc. 1959;70:103–114. [PMC free article] [PubMed] [Google Scholar]
  14. FESSLER J. H., COOPER K. E., CRANSTON W. I., VOLLUM R. L. Observations on the production of pyrogenic substances by rabbit and human leucocytes. J Exp Med. 1961 Jun 1;113:1127–1140. doi: 10.1084/jem.113.6.1127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. HANKS J. H., WALLACE J. H. Determination of cell viability. Proc Soc Exp Biol Med. 1958 May;98(1):188–192. doi: 10.3181/00379727-98-23985. [DOI] [PubMed] [Google Scholar]
  16. HARRIS H. Role of chemotaxis in inflammation. Physiol Rev. 1954 Jul;34(3):529–562. doi: 10.1152/physrev.1954.34.3.529. [DOI] [PubMed] [Google Scholar]
  17. HOLDSTOCK D. J., MATHIAS A. P., SCHACHTER M. A comparative study of kinin, kallidin, and bradykinin. Br J Pharmacol Chemother. 1957 Jun;12(2):149–158. doi: 10.1111/j.1476-5381.1957.tb00113.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. HURLEY J. V., SPECTOR W. G. Endogenous factors responsible for leucocytic emigration in vivo. J Pathol Bacteriol. 1961 Oct;82:403–420. doi: 10.1002/path.1700820218. [DOI] [PubMed] [Google Scholar]
  19. KAISER H. K., WOOD W. B., Jr Studies on the pathogenesis of fever. X. The effect of certain enzyme inhibitors on the production and activity of leucocvtic pvrogen. J Exp Med. 1962 Jan 1;115:37–47. doi: 10.1084/jem.115.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. KAISER H. K., WOOD W. B., Jr Studies on the pathogensis of fever. IX. The production of endogenous pyrogen by polymorphonuclear leucocytes. J Exp Med. 1962 Jan 1;115:27–36. doi: 10.1084/jem.115.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. KING M. K., WOOD W. B., Jr Studies on the pathogenesis of fever. IV. The site of action of leucocytic and circulating endogenous pyrogen. J Exp Med. 1958 Feb 1;107(2):291–303. doi: 10.1084/jem.107.2.291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. MARGOLIS J. Hagerman factor and capillary permeability. Aust J Exp Biol Med Sci. 1959 Jun;37:239–244. doi: 10.1038/icb.1959.24. [DOI] [PubMed] [Google Scholar]
  23. MARGOLIS J. The mode of action of Hageman factor in the release of plasma kinin. J Physiol. 1960 May;151:238–252. doi: 10.1113/jphysiol.1960.sp006434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. MILES A. A., WILHELM D. L. Enzyme-like globulins from serum reproducing the vascular phenomena of inflammation. I. An activable permeability factor and its inhibitor in guinea-pig serum. Br J Exp Pathol. 1955 Feb;36(1):71–81. [PMC free article] [PubMed] [Google Scholar]
  25. MOSES J. M., ATKINS E. Studies on tuberculin fever. II. Observations on the role of endogenous pyrogen in tolerance. J Exp Med. 1961 Dec 1;114:939–959. doi: 10.1084/jem.114.6.939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ponder E., Macleod J. WHITE CELL MORPHOLOGY IN RABBITS WITH INDUCED PERITONEAL EXUDATES. J Exp Med. 1938 May 31;67(6):839–846. doi: 10.1084/jem.67.6.839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. RAFTER G. W., COLLINS R. D., WOOD W. B., Jr Studies on the pathogenesis of fever. VII. Preliminary chemical characterization of leucocytic pyrogen. J Exp Med. 1960 Jun 1;111:831–840. doi: 10.1084/jem.111.6.831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. RATNOFF O. D., LEPOW I. H. COMPLEMENT AS A MEDIATOR OF INFLAMMATION. ENHANCEMENT OF VASCULAR PERMEABILITY BY PURIFIED HUMAN C'1 ESTERASE. J Exp Med. 1963 Nov 1;118:681–698. doi: 10.1084/jem.118.5.681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. SPECTOR W. G., STOREY E. A factor in the oestrogen-treated uterus responsible for leucocyte emigration. J Pathol Bacteriol. 1958 Apr;75(2):387–398. doi: 10.1002/path.1700750217. [DOI] [PubMed] [Google Scholar]
  30. SPECTOR W. G. Substances which affect capillary permeability. Pharmacol Rev. 1958 Dec;10(4):475–505. [PubMed] [Google Scholar]
  31. STETSON C. A., GOOD R. A. Studies on the mechanism of the Shwartzman-phenomenon; evidence for the participation of polymorphonuclear leucocytes in the phenomenon. J Exp Med. 1951 Jan;93(1):49–63. doi: 10.1084/jem.93.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. STETSON C. A., Jr Similarities in the mechanisms determining the Arthus and Shwartzman phenomena. J Exp Med. 1951 Oct;94(4):347–358. doi: 10.1084/jem.94.4.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. WILHELM D. L., MASON B. Vascular permeability changes in inflammation: the role of endogenous permeability factors in mild thermal injury. Br J Exp Pathol. 1960 Oct;41:487–506. [PMC free article] [PubMed] [Google Scholar]
  34. WOOD W. B., Jr Studies on the cause of fever. N Engl J Med. 1958 May 22;258(21):1023–1031. doi: 10.1056/NEJM195805222582101. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES