HUMAN MONOCYTES PRODUCE MONOCYTE CHEMOATTRACTANT PROTEIN-1 (MCP-1) INRESPONSE TO A SYNTHETIC PEPTIDE DERIVED FROM C-REACTIVE PROTEIN

We reported previously that a synthetic peptide (RS-83277) derived fro m human C-reactive protein (CRP) augmented human monocyte/macrophage t umoricidal activity and cytokine production. RS-83287, a synthetic pep tide derived from a different CRP site, was ineffective. Because chemo attractant properties have been attributed to some CRP-derived peptide s, we hypothesized that RS-83277, in addition to activating effects, m ight promote human monocyte chemotaxis. Results indicated that neither CRP peptide RS-83277 nor RS-83287 was, itself, a chemoattractant. RS- 83277, but not RS-83287, however, elicited time-dependent production o f monocyte chemoattractant activity in conditioned media (CM) of cultu red human mononuclear leukocytes and purified, adherent monocytes (RIG ). CM from nonadherent MO contained no activity, indicating that adher ence was required for monocyte response. Monocyte chemoattractant acti vity was dose-dependent and was removed by treatment with immobilized antibody to human monocyte chemoattractant protein 1 (MCP-1) but not b y irrelevant IgG. These results indicate that a specific peptide segme nt of CRP acts upon human adherent monocytes to promote production of the autocrine chemotactic and activating factor MCP-1. Data suggest th at degraded CRP represents a complex source of biologically active pep tides which, among other effects, may amplify monocyte recruitment to sites of injury, (C) 1995 Academic Press, Inc.