Proteolysis of human C-reactive protein produces peptides with potent immunomodulating activity.
We have studied the ability of human C-reactive protein to modulate the immune response in vitro. Whereas native C-reactive protein did not induce phagocytic leukocytes to chemotax or to produce superoxide, treatment of purified C-reactive protein with human neutrophil-derived acid proteases produced substances with potent effects on leukocyte function. Close examination of the primary structure of human C-reactive protein revealed three regions evenly distributed throughout the protein each of which contain peptide sequences closely resembling the amino acid sequence of the immunomodulator peptide tuftsin, Thr-Lys-Pro-Arg. We have synthesized the three peptides which include Thr-Lys-Pro-Leu ([Leu4]tuftsin), Gly-Lys-Pro-Arg ([Gly1]tuftsin), and Thr-Lys-Pro-Gln ([Gln4]tuftsin) and assayed them for biological activity. The three synthetic peptides were found to stimulate phagocytic leukocytes to chemotax, produce superoxide, and induce mononuclear cells to produce interleukin 1 in vitro at concentrations similar to those concentrations required for tuftsin to induce these phenomena. These results support a potentially important role for C-reactive protein as a possible immunomodulator during inflammation.
D000595:Amino Acid Sequence; D002097:C-Reactive Protein / Q000378:metabolism / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D009504:Neutrophils / Q000201:enzymology; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D010447:Peptide Hydrolases / Q000378:metabolism; D010586:Phagocytes / Q000378:metabolism; D013481:Superoxides / Q000097:blood; D014405:Tuftsin / Q000494:pharmacology
D007375:Interleukin-1; D010446:Peptide Fragments; D013481:Superoxides; D002097:C-Reactive Protein; D010447:Peptide Hydrolases; D014405:Tuftsin