C-reactive protein in myocardial infarction binds to circulating microparticles but is not associated with complement activation.
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.


OBJECTIVE
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.
Department of Cardiology, Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. p.m.vanderzee@amc.uva.nl
P M
PM
van der Zee
E
E
Biró
L A
LA
Trouw
Y
Y
Ko
R J
RJ
de Winter
C E
CE
Hack
A
A
Sturk
R
R
Nieuwland
D002097:C-Reactive Protein / Q000378:metabolism*; D002469:Cell Separation; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D003167:Complement Activation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism*
D007074:Immunoglobulin G; D002097:C-Reactive Protein