C-reactive protein-induced colony-stimulating factors production by macrophages

Purified human C-reactive protein(CRP: 0.5-50.0 micrograms/kg) given intravenously to monkeys (Macaca mulatta) induced serum colony-stimulating activity (CSF); maximum induction occurred at 10.0 micrograms/kg. In vitro also, purified human CRP (0.1-50.0 micrograms/ml) stimulated monkey blood monocyte-derived macrophages to release CSF in to the medium (CM); 5.0 micrograms/ml CRP appeared optimal. Both in vivo and in vitro, the kinetics of the production of CSF were similar with maximal response occurring 6 h after stimulation and return to background levels by 48 h. Rabbit anti-CRP antibody completely abrogated the production of CSFs in vitro, suggesting a specific interaction between CRP and macrophages. A neutralizing concentration of rabbit anti-human interleukin-1 (IL-1) polyclonal antibody had no effect on CRP induction of CSF-activity, indicating it to be IL-1 independent. CRP-induced CSFs, both in the serum and CM, were functionally similar as they supported the formation of granulocyte (G), macrophage (M) and GM colonies, in similar proportions. The macrophage production of CSFs appeared to be lipopolysaccharide-independent as polymyxin B (25.0 micrograms/ml) had no inhibitory effect. Heat-treated (80 degrees C, 1 h, pH 7.0) CRP did not stimulate the macrophages to produce CSFs. The CSF release was dependent on protein synthesis as it was completely inhibited by cycloheximide (50.0 micrograms/ml). This study demonstrates that purified human CRP can induce the production of serum CSF activity in monkeys, and can stimulate monkey macrophages to produce CSFs in vitro.