Binding of C-reactive protein to human neutrophils. Inhibition of respiratory burst activity.
We investigated the binding of highly purified soluble human C-reactive protein (CRP) to human neutrophils. Binding of CRP to neutrophils was rapid (50% of maximal binding occurred within 15 seconds), and complete within 5 minutes. Binding was inhibitable by excess unlabeled CRP, and nonspecific binding in the presence of a 200-fold excess of unlabeled CRP was 10% of total binding. Binding was not affected by other proteins, including albumin, fibronectin, rabbit IgG, or normal human plasma. Maximal binding required both calcium (0.5 mM) and magnesium (0.24 mM) ions. Calcium phosphorylcholine (10 micrograms/ml) or sodium citrate (10 micrograms/ml) completely dissociated bound CRP. Binding was saturable and most consistent with a 2-site model, demonstrating both a high-affinity receptor (1.4 x 10(4) sites/cell; Kd 3.7 x 10(-10) M) and a low-affinity receptor (4.2 x 10(5) sites/cell; Kd 2.5 x 10(-8) M). CRP at concentrations of 50 micrograms/ml inhibited the neutrophil superoxide production induced by phorbol ester. At concentrations of 100 micrograms/ml or greater, CRP also inhibited superoxide production in a cell-free xanthine oxidase-acetaldehyde system. These data suggest that CRP can down-regulate neutrophil oxidative capacity through interaction with receptors on neutrophils as well as by direct antioxidant activity.
Dobrinich
R
R
Department of Medicine, Cleveland Metropolitan General Hospital, Case Western Reserve University School of Medicine, Ohio.
Spagnuolo
P J
PJ
D002097:C-Reactive Protein / Q000378:metabolism*; D002118:Calcium / Q000502:physiology; D002951:Citrates / Q000494:pharmacology; D019343:Citric Acid; D015536:Down-Regulation / Q000502:physiology; D006801:Humans; D008274:Magnesium / Q000502:physiology; D009504:Neutrophils / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010703:Phorbol Esters / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
D002951:Citrates; D010703:Phorbol Esters; D013481:Superoxides; D019343:Citric Acid; D002097:C-Reactive Protein; D008274:Magnesium; D002118:Calcium