By CAROLYN MOLD , SHUEI NAKAYAMA , TIMOTHY

C-reactive protein (CRP) 1 is an acute phase serum protein produced rapidly in response to inflammatory stimuli. The binding and functional characteristics of CRP suggest that it may play a role in host defense against infection. CRP has binding specificity for the phosphocholine (PC) determinant of cell wall C-polysaccharide (PnC) from Streptococcus pneumoniae (1, 2). The binding of CRP to PnC can lead to C activation in human serum by the classical pathway (3). We have found CRP binding and C activation by intact S. pneumoniae of several different serotypes (unpublished observations). CRP in the presence of human C has been shown to opsonize PnC-sensitized erythrocytes (E-PnC) for phagocytosis by human monocytes (4) and mouse macrophages (5). We have extended these studies by demonstrating opsonization of mouse E-PnC by CRP in a mouse in vivo clearance model (6). Opsonization in this system resulted in increased splenic localization of E-PnC and required the presence of both CRP and mouse C. Despite these findings with E-PnC, the effectiveness of CRP as a bacterial opsonin has been uncertain. Earlier in vitro studies of phagocytosis have been conflicting (7-9). In an in vivo study, an association was reported between elevated levels of CRP and increased resistance to Staphylococcus aureus infection in endotoxin-treated mice (10). We have found an enhanced phagocytic response by human neutrophils to CRPand C-treated S. pneumoniae type 27 that has capsular as well as cell wall PC determinants. 2 Recently Briles et al. (11) reported that IgM antibody to PC can protect CBA/N mice against intravenous challenge with type 3 S. pneumoniae (Pn3). Since CRP shares the binding specificity and opsonic activity of IgM antibody to PC, it might be expected to provide similar protection. We have found that pretreatment with CRP can increase survival of mice infected with Pn3 or type 4 S. pneumoniae (Pn4). This effect was evident in normal BALB/c mice and in mice unable to produce antibody to PC because of neonatal tolerance induction. This study provides direct evidence of the effectiveness of CRP in host defense against pneumococcal infection.