PubMed · 9206803
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J M Porcel-Pérez, D Vergani. 1996. [Complement evaluation in the laboratory].. https://pubmed.ncbi.nlm.nih.gov/9206803/
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Activation of the complement system plays a key role in normal inflammatory response to injury but may cause substantial injury when activated inappropriately. The cascade is activated through classical, alternative and lectin pathways. The human complement system is in most cases well controlled by the host, and inappropriate activation and host cell destruction are prevented. The control is mainly mediated by complement regulatory proteins. The use of powerful methodologies in molecular biology, biochemistry and physiology has led to impressive advances in our knowledge of the mechanisms of complement activation and regulation and its role as either a protective or pathogenic factor in human disease. With respect to disease pathogenesis, the complexity of the cascades provides opportunities for several different therapeutic targets within the pathways, and we are about to witness the availability of a variety of complement modulators for specific therapies. This article reviews biological aspects of this important immunological effector mechanism.
Cardiopulmonary bypass (CPB) exposes blood to large, foreign surfaces. This exposure may activate the cellular and humoral inflammatory systems, resulting in inflammatory reactions and organ dysfunction. Coating the inner surfaces of the bypass circuit may help alleviate these side-effects. The objective of this study was to determine the influence of two new surface treatments on blood cell and complement activation. Oxygenator and tubing sets coated with synthetic polymers (n = 7) or heparin (n = 7) were compared to uncoated sets (n = 7) in an in vitro model of CPB. The circuits were run at 4 l/min and recirculated for 120 min. The inflammatory response was assessed at regular intervals by platelet counts, and activation of complement, leucocytes and platelets. We found that the median platelet counts decreased from 127 to 122 x 10(9)/l (not significant, NS) in the synthetic polymer sets, from 96 to 88 x 10(9)/l (NS) in the heparin-coated sets, and from 93 to 54 x 10(9)/l (p < 0.01) in the uncoated sets after 2 h of recirculation. There were significant differences in platelet counts between the coated sets and the uncoated set at end of experiments (p < 0.05). Beta-thromboglobulin (BTG) concentrations increased in the synthetic polymer sets from 166 to 352 ng/ml (p < 0.01), in the heparin coated sets from 336 to 1168 ng/ml (p < 0.01), and in the uncoated sets from 301 to 3149 ng/ml (p < 0.01) after 2 h of recirculation. The differences in BTG at termination of the experiments were significant among all three sets (p < 0.05). Myeloperoxidase (MPO) concentrations in the synthetic polymer sets increased from 63 to 86 micrograms/l (p < 0.01), in the heparin-coated sets from 90 to 208 micrograms/l (p < 0.01), and in the uncoated sets from 122 to 513 micrograms/l (p < 0.01) after 2 h of recirculation. The differences in MPO at termination of the experiments were significant among all three groups (p < 0.01). There were no significant differences at termination of the experiments among the three sets regarding complement activation as measured by C3 activation products and the terminal complement complex. We conclude that in the current in vitro model of a CPB circuit, the synthetic polymer coating and the heparin coating caused significantly less platelet loss and granulocyte and platelet activation than the uncoated surface (p < 0.05). The synthetic polymer coating caused significantly less granulocyte and platelet activation than the heparin coating (p < 0.05). There was moderate complement activation within each group, but no significant differences among the three groups.
The activation of inflammation and coagulation cascades is part of the pathogenesis of adult respiratory distress syndrome (RDS). Previous studies have demonstrated contact activation in preterm infants with RDS, whereas no concordant results have been found with complement activation. In this study, both systems were investigated in preterm infants with severe RDS and related to surfactant response. Thirty preterm newborns with severe respiratory distress (FiO2 > 0.5), but with no evidence of infection or fetal acidosis, were studied. Eighteen healthy preterm newborns of similar gestational age and birth weight served as controls. The study group was divided into two subgroups, according to their response to a porcine natural surfactant 6 h after administration: responders (FiO2 reduction > 50%) and poor responders (FiO2 reduction < or = 50%). C1q, C4, factor B, C3a, C5a, complement, and C1-inhibitor activity, as well as factor XIIa, were determined in blood samples, drawn 24 h after birth. Except for C1-inhibitor concentration and C1-inhibitor activity, all parameters for infants with severe RDS were different from controls. Complement precursor proteins were lower, and activated split products of the complement and contact system were higher. Infants with a poor response after application of surfactant showed higher amounts of C3a, C5a, and factor XIIa but lower C1q and C4 levels compared with infants with a good response to surfactant. Activation of the complement and the contact system was demonstrated in all respiratory distress patients. This activation was more pronounced in poor responders to exogenous surfactant.