Activation of human monocytes and alveolar macrophages by a synthetic peptide of C-reactive protein.
We have previously shown that native human C-reactive protein (CRP) produces antitumor effects in experimental animals, and that these effects are mediated primarily through macrophages. More recently, we have observed that RS-83277, a synthetic peptide derived from CRP, appears to mimic the antitumor effects of native CRP. The purpose of this study was to determine the effects of RS-83277 on normal human monocyte and alveolar macrophage tumoricidal activity, and cytokine secretion. At optimal doses of 250-500 micrograms/ml, RS-83277 significantly enhanced tumoricidal activity of both monocytes and macrophages. RS-83287, a CRP peptide derived from a different site, had no effect at these doses. Specificity of RS-83277 for monocyte/macrophage-mediated cytotoxic activity was demonstrated by the failure of RS-83277 to enhance either natural killer (NK) or lymphokine-activated killer (LAK) cell-mediated activity. RS-83277 also augmented secretion of interleukin-1-beta (IL-1 beta) and interleukin-6 (IL-6) by monocytes. These data suggest a role for synthetic CRP peptide, RS-83277, as a novel biological response modifier in cancer therapy.
Thomassen
M J
MJ
Department of Pulmonary and Critical Care Medicine, Cleveland Clinic Foundation, OH 44195-5038.
Meeker
D P
DP
Deodhar
S D
SD
Wiedemann
H P
HP
Barna
B P
BP
D002097:C-Reactive Protein / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008262:Macrophage Activation / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D010455:Peptides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D007155:Immunologic Factors; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D010455:Peptides; C079718:RS 83277; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein