Complement activation and polymorphonuclear neutrophil leukocyte elastase in sepsis. Correlation with severity of disease.

Abstract

Complement activation is necessary for an adequate immune and inflammatory response to infections. Activation releases anaphylatoxins that cause vasodilation, increase vascular permeability, and trigger release of polymorphonuclear neutrophil leukocyte (PMN) lysosomal enzyme and oxygen radicals. Under normal circumstances, an orderly progression of such events has a beneficial antimicrobial effect. The same mechanism, however, when uncontrolled, may damage host tissues. To provide information about the clinical importance of such events in sepsis, different complement parameters (C3, C4, and the desarginated forms of C3a [C3a(des)-Arg] and C5a [C5a(des)-Arg]), PMN elastase, and malondialdehyde (a by-product of membrane peroxidation by oxygen radicals) were measured daily in 26 septic patients and correlated with two objectively assessed and previously validated severity scores (acute physiology and chronic health evaluation [APACHE II] and Sepsis Severity Score [SSS]). Nonsurvivors (n = 12) had significantly greater and longer lasting complement activation than that in survivors, as reflected by higher levels of catabolic peptides (C3a(des)-Arg) and lower levels of native proteins (C3 and C4). C3a(des)-Arg, C3, C4, and the C3a(des)-Arg-C3 ratio were correlated with Sepsis Severity Scores. Polymorphonuclear neutrophil leukocyte elastase levels were higher in nonsurvivors and were correlated with C3a(des)-Arg and the C3a(des)-Arg-C3 ratio. Malondialdehyde levels were significantly higher in all patients than in controls, without, however, any relationship to severity of disease or clinical outcome. Since the higher and more persistent the complement activation and polymorphonuclear neutrophil leukocyte stimulation, the worse the patient's prognosis, we conclude that these mechanisms may be important in the clinical development of sepsis.

• Authors: M Gardinali, P Padalino, S Vesconi, A Calcagno, S Ciappellano, L Conciato, O Chiara, A Agostoni, A Nespoli
• Journal: Archives of surgery (Chicago, Ill. : 1960) (Arch Surg) Vol. 127 Issue 10 Pg. 1219-24 (Oct 1992) ISSN: 0004-0010 [Print] United States
• PMID: 1417490 (Publication Type: Journal Article)

Chemical References

• Anaphylatoxins
• Complement C3
• Complement C4
• Complement C5a, des-Arginine
• alpha 1-Antitrypsin
• complement C3a, des-Arg-(77)-
• Malondialdehyde
• Complement C3a
• Pancreatic Elastase
• Leukocyte Elastase

Topics

• Adult
• Aged
• Anaphylatoxins (analysis)
• Bacterial Infections (blood, enzymology, immunology)
• Cell Degranulation (immunology)
• Cell Membrane (ultrastructure)
• Complement Activation (physiology)
• Complement C3 (analysis)
• Complement C3a (analogs & derivatives, analysis)
• Complement C4 (analysis)
• Complement C5a, des-Arginine (analysis)
• Female
• Humans
• Leukocyte Elastase
• Male
• Malondialdehyde (analysis, blood)
• Middle Aged
• Multiple Organ Failure (immunology)
• Neutrophils (enzymology, pathology)
• Pancreatic Elastase (analysis, antagonists & inhibitors, blood)
• Severity of Illness Index
• Survival Rate
• alpha 1-Antitrypsin (analysis)