C-REACTIVE PROTEIN-INDUCED COLONY-STIMULATION FACTORS PRODUCTION BY MACROPHAGES

Purified human C-reactive protein(CRP: 0.5 - 50.0 mu g/kg) given intra venously to monkeys (Macaca mulatta) induced serum colony-stimulating activity (CSF); maximum induction occurred at 10.0 mu g/kg. In vitro a lso, purified human CRP (0.1 - 50.0 mu g/ml) stimulated monkey blood m onocyte-derived macrophages to release CSF in to the medium (CM); 5.0 mu g/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 neu tralizing concentration of rabbit anti-human interleukin-1 (IL-1) poly clonal antibody had no effect on CRP induction of CSF-activity, indica ting it to be IL-1 independent, CRP-induced CSFs, both in the serum an d CM, were functionally similar as they supported the formation of gra nulocyte (G), macrophage (M) and GM colonies, in similar proportions, The macrophage production of CSFs appeared to be lipopolysaccharide-in dependent as polymyxin B (25.0 mu g/ml) had no inhibitory effect, Heat -treated (80 degrees C, 1 h, pH 7.0) CRP did not stimulate the macroph ages to produce CSFs. The CSF release was dependent on protein synthes is as it was completely inhibited by cycloheximide (50.0 mu g/ml) This study demonstrates that purified human CRP can induce the production of serum CSI: activity in monkeys, and can stimulate monkey macrophage s to produce CSFs in vitro.