A role for C-reactive protein in the complement-mediated stimulation of human neutrophils by type 27 Streptococcus pneumoniae.
Although C-reactive protein (CRP) has been shown to be opsonic when bound to erythrocytes, its role in bacterial phagocytosis is unclear. Chemiluminescence (CL), a measure of the metabolic stimulation of neutrophils, was used to investigate the effects of CRP and complement (C) on the interaction between phagocytes and Streptococcus pneumoniae, type 27 (Pn27). CRP binding to Pn27 was demonstrated by using radiolabeled CRP, and Scatchard analysis indicated a saturation binding of about 10(7) CRP molecules/CFU. When Pn27 was pretreated with normal human serum and added to neutrophils, the CL response observed was directly related to the number of bacteria and the amount of serum added. Although bacteria pretreated with CRP alone produced minimal CL, the addition of CRP to serum resulted in a two to 13-fold enhancement of the CL response. CRP enhancement of CL was not observed with heated serum or serum from a patient genetically lacking C2. CRP bound to Pn27 was found to cause consumption of C3 and C4 in normal human serum, indicating activation of the classical C pathway. Because CRP opsonization might provide early protection in the nonimmune host, we tested the ability of CRP to enhance opsonization in serum with markedly decreased immunoglobulin. CRP enhanced the CL response in serum from a hypogammaglobulinemic patient to between 12 and 16 times the serum control. These studies show CRP binds to Pn27 and in the presence of C enhances the opsonization of these organisms. These findings support the concept that CRP plays a protective role in bacterial infection.
D000361:Agammaglobulinemia / Q000276:immunology; D001665:Binding Sites; D002097:C-Reactive Protein / Q000276:immunology* / Q000378:metabolism; D003176:Complement C3 / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D003171:Complement Pathway, Classical; D003165:Complement System Proteins / Q000378:metabolism*; D006801:Humans; D009504:Neutrophils / Q000276:immunology*; D009895:Opsonin Proteins / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology*
D003176:Complement C3; D003181:Complement C4; D009895:Opsonin Proteins; D003165:Complement System Proteins; D002097:C-Reactive Protein