Serum amyloid P-component-induced colony-stimulating factors production by macrophages

Abstract

Purified mouse serum amyloid P-component (SAP; 0.5-50 μg/kg), injected intravenously into Swiss mice, induced the production of serum colony-stimulating factors (CSFs); the maximum induction was observed at 10.0 μg/kg. Further, in vitro purified mouse SAP (0.1-50 μg/ml) stimulated the mouse elicited peritoneal macrophages to elaborate CSFs in the conditioned medium (CM); 5.0 μg/ml SAP appeared to be the optimum. Both in vivo and in vitro the maximum production of CSFs occurred 6 h after initiation of stimulation, and returned to the background levels by 48 h. Mannose 6-P, mannose 1-P and mannose, and not other sugars inhibited the SAP-induced production of CSFs by macrophages which suggests that SAP interaction with macrophages was mediated by specific glycoprotein-receptors. A neutralizing (100%) concentration of rabbit antimouse interleukin (IL)-1 polyclonal antibody had no effect on the SAP-induced CSF production, indicating that it would be IL-1-independent. SAP-induced CSFs, both in serum and CM, were functionally similar as they supported the formation of granulocyte (G), macrophage (M) and GM colonies in similar proportions. The production of CSFs appeared to be lipopolysaccharide (LPS)independent as it was not inhibited by polymyxin B sulfate (25.0 μg/ml), and heat-inactivated (80 °C, 1 h, pH 7.0) SAP did not induce the production of CSFs. The CSFs were produced de novo because cylcoheximide (50.0 μg/ml) completely inhibited their production. These results demonstrate that purified mouse SAP, in a dose-dependent manner, can induce the production of serum CSFs in mice, and can induce LPS-independent de novo production of CSFs by elicited macrophages in vitro.