Abstract
Human monocytes and neutrophils were separated from buffy coats of blood obtained from normal donors. Following incubation with heat-killed staphylococci, monocyte preparations contained 20 times more pyrogenic activity in the supernatant media than did supernates from an equal number of neutrophils. During purification of these pyrogens it was discovered that these cell preparations each produced a distinct and different pyrogen. The pyrogen obtained from neutrophils had a mol wt of 15,000 following Sephadex G-75 gel filtration, an isoelectric point of 6.9, and could be precipitated and recovered from 50% ethanol at –10°C. In contrast, the pyrogen derived from monocyte preparations had a mol wt of 38,000, an isoelectric point of 5.1, and was destroyed in cold ethanol. Both molecules were unaffected by viral neuraminidase but biologically destroyed at 80°C for 20 min and with trypsin at pH 8.0. The febrile peak produced by partially purified neutrophil pyrogen occurred at 40 min while that from monocytes was at 60 min. In addition, monocyte pyrogen produced more sustained fevers for the same peak elevation as neutrophil pyrogen. These studies demonstrate for the first time two chemically and biologically distinctive pyrogens derived from circulating human white blood cells and have important implications for our understanding of the pathogenesis of fever in man.
Full Text
The Full Text of this article is available as a PDF (665.0 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Atkins E., Bodel P. Fever. N Engl J Med. 1972 Jan 6;286(1):27–34. doi: 10.1056/NEJM197201062860109. [DOI] [PubMed] [Google Scholar]
- Bodel P. T., Wechsler A., Atkins E. Comparison of endogenous pyrogens from human and rabbit leucocytes utilizing Sephadex filtration. Yale J Biol Med. 1969 Apr;41(5):376–387. [PMC free article] [PubMed] [Google Scholar]
- Bodel P., Atkins E. Human leukocyte pyrogen producing fever in rabbits. Proc Soc Exp Biol Med. 1966 Mar;121(3):943–946. doi: 10.3181/00379727-121-30931. [DOI] [PubMed] [Google Scholar]
- Bodel P., Atkins E. Release of endogenous pyrogen by human monocytes. N Engl J Med. 1967 May 4;276(18):1002–1008. doi: 10.1056/NEJM196705042761803. [DOI] [PubMed] [Google Scholar]
- Bodel P. Studies on the mechanism of endogenous pyrogen production. I. Investigation of new protein synthesis in stimulated human blood leucocytes. Yale J Biol Med. 1970 Dec;43(3):145–163. [PMC free article] [PubMed] [Google Scholar]
- Felgenhauer K., Pak S. J. Detection of Ampholine patterns. Ann N Y Acad Sci. 1973 Jun 15;209:147–153. doi: 10.1111/j.1749-6632.1973.tb47525.x. [DOI] [PubMed] [Google Scholar]
- Moore D. M., Murphy P. A., Chesney P. J., Wood W. B., Jr Synthesis of endogenous pyrogen by rabbit leukocytes. J Exp Med. 1973 May 1;137(5):1263–1274. doi: 10.1084/jem.137.5.1263. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nordlund J. J., Root R. K., Wolff S. M. Studies on the origin of human leukocytic pyrogen. J Exp Med. 1970 Apr 1;131(4):727–743. doi: 10.1084/jem.131.4.727. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Radola B. J. Analytical and preparative isoelectric focusing in gel-stabilized layers. Ann N Y Acad Sci. 1973 Jun 15;209:127–143. doi: 10.1111/j.1749-6632.1973.tb47523.x. [DOI] [PubMed] [Google Scholar]
- Rafter G. W., Cheuk S. F., Krause D. W., Wood W. B., Jr Studies on the pathogenesis of fever. XIV. Further observations on the chemistry of leukocytic pyrogen. J Exp Med. 1966 Mar 1;123(3):433–444. doi: 10.1084/jem.123.3.433. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Root R. K., Nordlund J. J., Wolff S. M. Factors affecting the quantitative production and assay of human leukocytic pyrogen. J Lab Clin Med. 1970 Apr;75(4):679–693. [PubMed] [Google Scholar]
- Root R. K., Wolff S. M. Pathogenetic mechanisms in experimental immune fever. J Exp Med. 1968 Aug 1;128(2):309–323. doi: 10.1084/jem.128.2.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
- WARREN L. The thiobarbituric acid assay of sialic acids. J Biol Chem. 1959 Aug;234(8):1971–1975. [PubMed] [Google Scholar]
- 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]