Abstract
Sepsis syndrome (SS) is associated with depressed PAF acetylhydrolase, the enzyme responsible for the degradation of platelet activating factor. PAF acetylhydrolase is in a large part produced by macrophages, whose inadequate activation with haemophagocytosis is frequent in patients with SS. The aim of this study was to test the hypothesis that PAF acetylhydrolase levels could be affected in these critically ill patients, because of the large amounts produced by activated macrophages in vitro and in vivo in animal models. The levels of serum PAF acetylhydrolase were assessed in 90 SS patients, who were divided into three groups: patients with (n = 34) or without haemophagocytosis (n = 31), and patients without thrombocytopenia (n = 25) who were used as a control group. The number of organ dysfunctions was matched between patients with haemophagocytosis and controls. Normal reference values were obtained in 59 randomly selected blood donors. Circulating levels of PAF acetylhydrolase were significantly (p = 0.0001) decreased in patients with SS (57+/-3 nmol/ml/min, n = 90) when compared with healthy subjects (69+/-3 nmol/ml/min, n = 59). PAF acetylhydrolase levels were greater in the presence of a haemophagocytosis but without statistical significance (64.2+/-6.5 vs. 50.1+/-2.8:p = 0.25). Despite the fact that macrophagic activation stimulates the in vitro release of PAF acetylhydrolase, no difference was found between patients with or without haemophagocytosis. The mechanism and the role of the PAF acetylhydrolase reduction in SS patients remain to be determined.
Full Text
The Full Text of this article is available as a PDF (130.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ambrosio G., Oriente A., Napoli C., Palumbo G., Chiariello P., Marone G., Condorelli M., Chiariello M., Triggiani M. Oxygen radicals inhibit human plasma acetylhydrolase, the enzyme that catabolizes platelet-activating factor. J Clin Invest. 1994 Jun;93(6):2408–2416. doi: 10.1172/JCI117248. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Asano K., Okamoto S., Fukunaga K., Shiomi T., Mori T., Iwata M., Ikeda Y., Yamaguchi K. Cellular source(s) of platelet-activating-factor acetylhydrolase activity in plasma. Biochem Biophys Res Commun. 1999 Aug 2;261(2):511–514. doi: 10.1006/bbrc.1999.1066. [DOI] [PubMed] [Google Scholar]
- Beal A. L., Cerra F. B. Multiple organ failure syndrome in the 1990s. Systemic inflammatory response and organ dysfunction. JAMA. 1994 Jan 19;271(3):226–233. [PubMed] [Google Scholar]
- Bone R. C., Balk R. A., Cerra F. B., Dellinger R. P., Fein A. M., Knaus W. A., Schein R. M., Sibbald W. J. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992 Jun;101(6):1644–1655. doi: 10.1378/chest.101.6.1644. [DOI] [PubMed] [Google Scholar]
- Dupuis F., Levasseur S., Jean-Louis F., Dulery C., Praloran V., Denizot Y., Michel L. Production, metabolism and effect of platelet-activating factor on the growth of the human K562 erythroid cell line. Biochim Biophys Acta. 1997 Dec 12;1359(3):241–249. doi: 10.1016/s0167-4889(97)00106-7. [DOI] [PubMed] [Google Scholar]
- Elstad M. R., Stafforini D. M., McIntyre T. M., Prescott S. M., Zimmerman G. A. Platelet-activating factor acetylhydrolase increases during macrophage differentiation. A novel mechanism that regulates accumulation of platelet-activating factor. J Biol Chem. 1989 May 25;264(15):8467–8470. [PubMed] [Google Scholar]
- Elstad M. R., Stafforini D. M., Prescott S. M., McIntyre T. M., Zimmerman G. A. Human macrophages secrete platelet-activating factor acetylhydrolase. A mechanism for resolution of pulmonary inflammation. Chest. 1991 Mar;99(3 Suppl):9S–10S. doi: 10.1378/chest.99.3_supplement.9s. [DOI] [PubMed] [Google Scholar]
- Fagon J. Y., Chastre J., Novara A., Medioni P., Gibert C. Characterization of intensive care unit patients using a model based on the presence or absence of organ dysfunctions and/or infection: the ODIN model. Intensive Care Med. 1993;19(3):137–144. doi: 10.1007/BF01720528. [DOI] [PubMed] [Google Scholar]
- François B., Trimoreau F., Vignon P., Fixe P., Praloran V., Gastinne H. Thrombocytopenia in the sepsis syndrome: role of hemophagocytosis and macrophage colony-stimulating factor. Am J Med. 1997 Aug;103(2):114–120. doi: 10.1016/s0002-9343(97)00136-8. [DOI] [PubMed] [Google Scholar]
- Graham R. M., Stephens C. J., Silvester W., Leong L. L., Sturm M. J., Taylor R. R. Plasma degradation of platelet-activating factor in severely ill patients with clinical sepsis. Crit Care Med. 1994 Feb;22(2):204–212. doi: 10.1097/00003246-199402000-00009. [DOI] [PubMed] [Google Scholar]
- Knaus W. A., Draper E. A., Wagner D. P., Zimmerman J. E. APACHE II: a severity of disease classification system. Crit Care Med. 1985 Oct;13(10):818–829. [PubMed] [Google Scholar]
- Memon R. A., Fuller J., Moser A. H., Feingold K. R., Grunfeld C. In vivo regulation of plasma platelet-activating factor acetylhydrolase during the acute phase response. Am J Physiol. 1999 Jul;277(1 Pt 2):R94–103. doi: 10.1152/ajpregu.1999.277.1.R94. [DOI] [PubMed] [Google Scholar]
- Partrick D. A., Moore E. E., Moore F. A., Biffl W. L., Barnett C. C. Reduced PAF-acetylhydrolase activity is associated with postinjury multiple organ failure. Shock. 1997 Mar;7(3):170–174. doi: 10.1097/00024382-199703000-00003. [DOI] [PubMed] [Google Scholar]
- Stafforini D. M., Prescott S. M., Zimmerman G. A., McIntyre T. M. Platelet-activating factor acetylhydrolase activity in human tissues and blood cells. Lipids. 1991 Dec;26(12):979–985. doi: 10.1007/BF02536488. [DOI] [PubMed] [Google Scholar]