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Background: Inflammation plays a major role in the vascular dysfunction seen in preeclampsia, and several studies suggest involvement of the complement system. Objectives: To investigate whether complement activation on the surface of microparticles is increased in plasma of preeclamptic patients versus healthy pregnant controls. Methods: Microparticles from plasma of preeclamptic (n=10), healthy pregnant (n=10) and healthy nonpregnant (n=10) women were analyzed by flow cytometry for bound complement components (C1q, C4, C3) and complement activator molecules (C-reactive protein [CRP], serum amyloid P component [SAP], immunoglobulin [Ig]M, IgG). Fluid phase complement activation products and activator molecules were also determined. Results: Levels of microparticles with bound complement components showed no increase in complement activation on the microparticle surface in preeclamptic women, in line with levels of fluid phase complement activation products. In healthy nonpregnant and pregnant women, bound CRP was associated with classical pathway activation on the microparticle surface, and in healthy pregnant women IgM and IgG molecules also contributed. In preeclamptic women, microparticles with bound SAP and those with IgG seemed to contribute to C1q binding without a clear association to further classical pathway activation. Furthermore, significantly increased levels of microparticles with bound CRP were present in preeclamptic compared with healthy pregnant women (median 178x10(6)/L versus 47x10(6)/L, P<0.01), but without concomitant increases in complement activation. Conclusions: We found no evidence of increased complement activation on the microparticle surface in preeclamptic women. Microparticles with bound CRP were significantly increased, but in contrast to healthy pregnant and nonpregnant women, this was not associated with increased classical pathway activation on the surface of the microparticles. [ABSTRACT FROM AUTHOR]

Objective: Impaired perfusion of the myocardium induces a local inflammatory response. In animal models, there is ample evidence that polymorphonuclear leucocytes (PMNs) infiltrating infarcted myocardium contribute significantly to infarct size. Methods: To explore a possible role for PMNs in the tissue damage of human myocardial infarction, we investigated localization of intercellular adhesion molecule-1 (ICAM-1) and CD66b (previously clustered as CD67), a marker of degranulation of human PMNs, in relation to deposition of complement in tissue specimens of infarcted and healthy parts of the heart obtained from 20 patients, who had died following acute myocardial infarction. Results: ICAM-1 was transiently expressed by endothelium and for a longer period (few days) on myofibers of infarcted myocardium. This expression only occurred in parts that stained positive for complement. PMN infiltration exclusively occurred in areas with ICAM-1 expression, but not every ICAM-1-positive area contained PMN infiltrates. CD66b was found in PMNs but was also fixed to the plasma membrane of myofibers that stained positive for complement and ICAM-1. Conclusion: These findings indicate that, in infarcted human myocardium, PMNs are degranulated, possibly upon interaction with ICAM-1 and activated complement. [ABSTRACT FROM PUBLISHER]

Abstract: Background: C-reactive protein (CRP) is elevated in patients with acute myocardial infarction (AMI). When CRP binds to membrane phospholipids or Fc receptors, it activates the complement system. Recent studies show that CRP can be exposed on cell-derived microparticles (MP) and is associated complement activation. Objectives: We studied complement activation on circulating MP in AMI patients and healthy controls. Methods: MP were isolated from plasma of AMI patients (n =21) and sex- and age-matched healthy individuals (n =10), and analyzed by flow cytometry for bound complement components (C1q, C4, C3) and complement inhibitor and activator molecules (C4bp, CRP, serum amyloid P component, immunoglobulins IgM and IgG). Concurrently, the levels of fluid phase complement activation products and inhibitor and activator molecules were determined. Results: Fluid phase CRP, MP with bound CRP (CRP + MP), and C3 activation products were elevated in AMI patients compared to controls (P =0.032, P =0.031 and P =0.023, respectively), and fluid phase CRP correlated with CRP+ MP (r =0.84, P <0.001). Although CRP+ MP were elevated, they were not associated with C1q+ MP (r =0.32, P =0.174). In contrast, IgG+ MP were associated with C1q+ MP (r =0.73, P <0.001), C4+ MP and C3+ MP (r =0.78 and r =0.87, respectively; both P <0.001), and C4bp (r =0.63, P =0.004). In healthy individuals, CRP+ MP were strongly associated with C1q+ MP (r =0.82, P =0.007), which in turn were associated with C4+ MP and C3+ MP (r =0.68, P =0.032 and r =0.68, P =0.031, respectively). Conclusions: Despite CRP-associated complement activation on the surface of MP in healthy individuals and a strong correlation between MP-bound CRP and fluid phase CRP in AMI patients, the MP-associated complement activation is IgG- but not CRP-dependent in AMI patients. [Copyright &y& Elsevier]