Interactions of C-reactive protein with the complement system. III. Complement-dependent passive hemolysis initiated by CRP.

Abstract

Interactions of CRP with various substrates in the presence of human serum have been shown to result in efficient activation of C components C1-C5. We now report the ability of CRP to initiate C-dependent hemolysis. For this purpose CRP was isolated by affinity chromatography using pneumococcal CPS and gel filtration; its purity was established by several criteria. Erythrocytes were coated with CPS (E-CPS) and passively sensitized with CRP. C-dependent lysis of these cells was observed upon the addition of suitably absorbed human serum, and the efficiency of hemolysis compared favorably with that initiated by rabbit IgG anti-CPS antibody. CRP also sensitized E-CPS for lysis by guinea pig C; partial lysis was seen when C4-deficient guinea pig serum was used, suggesting that CRP also shares with antibody the ability of CRP to fully activate the C system and provide further evidence for a role for CRP similar to that of antibody in the initiation and modulation of inflammatory reactions via the complete system.

Characterization of C-reactive protein and the complement subcomponent C1t as homologous proteins displaying cyclic pentameric symmetry (pentraxins).

“…2e). it is therefore likely that the molecule consists of 5 and not of 10 protomers. This is distinct from the decameric, "doublet" structures described for Clt and amyloid P-component, which tend in addition to form rod-like stacks of several molecules (12)(13)(14), but it is consistent with the molecular weights of rabbit CRP and its subunit, 118,000 (8) Fig.…”

“…However, one of these agents, C-reactive protein (CRP), would appear to act in a manner entirely analogous to immunoglobulin. It has been found that upon interaction with a variety of substances, CRP can activate the C cascade and initiate both the opsonic and lytic potentials of this system through an activation of the primary C pathway (3)(4)(5)(6). CRP has been described as being comprised of probably identical subunits, ca 23,000 daltons, noncovalently linked to form an oligomer of molecular weight 120,000-140,000 (7,8).…”

“…Subunits and aggregates of CRP were removed from the native protein by gel filtration in Trisbuffered saline on Bio-Gel A-0.5m. The purity of such preparations of CRP has been previously established (5). Cyanogen bromide digestion of CRP was performed in 70% formic acid with a 500-fold molar excess of CNBr over methionyl residues for 18 hr at 22-24°, and the resultant peptides were fractionated in 6 M guanidinium chloride on Bio-Gel A-0.5m.…”

“…Human CRP was isolated by affinity chromatography of human serous fluids on agarose beads (Bio-Gel A-15m) to which pneumococcal C-polysaccharide was covalently linked (5). Subunits and aggregates of CRP were removed from the native protein by gel filtration in Trisbuffered saline on Bio-Gel A-0.5m.…”

Partial amino-acid sequences of human and rabbit C-reactive proteins: homology with immunoglobulins and histocompatibility antigens.

“…CRP was initially defined by a unique, calcium-dependent precipitation reaction with the pneumococcal C-polysaccharide (1,2). In addition, CRP is an agglutinin (3) and an opsonin (4), and, in the presence of a suitable ligand, CRP activates the complement system to cause depletion of complement component hemolytic activity (5)(6)(7) and promotion of complement-dependent opsonization (8) and hemolysis (9). This array of properties, reminiscent of specific antibody, has prompted us to postulate shared functions and a common evolutionary origin for CRP and immunoglobulins.…”