Gardinali M, Padalino P, Vesconi S, Calcagno A, Ciappellano S, Conciato L, Chiara O, Agostoni A, Nespoli A
University of Milan, Italy.
Arch Surg. 1992 Oct;127(10):1219-24. doi: 10.1001/archsurg.1992.01420100077014.
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.
补体激活对于针对感染产生充分的免疫和炎症反应是必要的。激活会释放过敏毒素，这些毒素会引起血管舒张、增加血管通透性，并触发多形核中性粒细胞（PMN）溶酶体酶和氧自由基的释放。在正常情况下，此类事件的有序进展具有有益的抗菌作用。然而，同样的机制在不受控制时可能会损害宿主组织。为了提供有关此类事件在脓毒症中临床重要性的信息，对26例脓毒症患者每天测量不同的补体参数（C3、C4以及C3a [C3a(des)-Arg]和C5a [C5a(des)-Arg]的去精氨酸形式）、PMN弹性蛋白酶和丙二醛（氧自由基引起的膜过氧化的副产物），并将其与两个经过客观评估且先前已验证的严重程度评分（急性生理学和慢性健康评估[APACHE II]和脓毒症严重程度评分[SSS]）相关联。非幸存者（n = 12）的补体激活程度明显更高且持续时间更长，这表现为分解代谢肽（C3a(des)-Arg）水平较高而天然蛋白（C3和C4）水平较低。C3a(des)-Arg、C3、C4以及C3a(des)-Arg - C3比值与脓毒症严重程度评分相关。非幸存者的多形核中性粒细胞弹性蛋白酶水平较高，且与C3a(des)-Arg和C3a(des)-Arg - C3比值相关。所有患者的丙二醛水平均显著高于对照组，但与疾病严重程度或临床结局均无关联。由于补体激活和多形核中性粒细胞刺激越高且越持久，患者的预后就越差，我们得出结论，这些机制可能在脓毒症的临床发展中起重要作用。
