ACTIVATION OF ALVEOLAR MACROPHAGE TNF AND MCP-1 EXPRESSION IN-VIVO BYA SYNTHETIC PEPTIDE OF C-REACTIVE PROTEIN

Administration of multilamellar vesicles (MLV) encapsulating a synthet ic peptide (RS-83277) derived from human C-reactive protein (CRP) augm ents anti-tumor activity of murine alveolar macrophages and reduces es tablished pulmonary metastases of experimental tumors. To explore mech anisms involved in these phenomena, we investigated cytokine and integ rin (CD11b) expression of bronchoalveolar lavage (BAL)-derived alveola r macrophages in control (blank MLV) and RS-83277-MLV-treated C57B1 mi ce, Alveolar macrophage production of tumor necrosis factor alpha (TNF -alpha) and monocyte chemoattractant bioactivity increased at 48 h aft er treatment with RS-83277-MLV but not control MLV, Chemoattractant ac tivity was neutralized by antibody to monocyte chemoattractant protein -1 (MCP-1), brit not irrelevant immunoglobulin G (IgG). Changes were r eflected by augmented TNF-alpha and MCP-1 mRNA levels in pulmonary tis sue and enhanced CD11b expression on mononuclear leukocytes derived fr om total lung tissue, but not on BAL-derived alveolar macrophages. Res ults suggest that RS-83277-MLV treatment is associated with activation of alveolar macrophage TNF-alpha and MCP-1 production and up-regulati on of adhesion molecules on pulmonary mononuclear leukocytes but not o n alveolar macrophages.