Effect of human C-reactive protein on chemokine and chemotactic factor-induced neutrophil chemotaxis and signaling.
C-reactive protein (CRP) is a unique serum pentraxin and the prototype acute phase reactant. CRP is a ligand for specific receptors on phagocytic leukocytes, and mediates activation reactions of monocytes/macrophages, but inhibits the respiratory burst of neutrophils (PMN). Since CRP selectively accumulates at inflammatory sites in which IL-8 is also produced, we tested the effects of CRP on the responsiveness of PMN to IL-8 and the bacterial chemotactic peptide, FMLP-phenylalanine (FMLPP). Purified human CRP inhibited the chemotactic response of PMN to IL-8 and FMLPP. A mouse IgM mAb that was generated against the leukocyte CRP receptor (CRP-R) also inhibited the chemotactic response. Incubation of purified CRP with activated PMN generated CRP-derived peptides that also inhibited chemotaxis. A synthetic CRP peptide (residues 27-38) that binds to the CRP-R had weak chemotactic activity, whereas two other CRP synthetic peptides (residues 174-185 and 191-205) inhibited chemotaxis of PMNs to both IL-8 and FMLPP. CRP did not alter receptor-specific binding of IL-8, but exerted its effect at the level of signaling. CRP augmented both IL-8- and FMLPP-induced mitogen-activated protein kinase (extracellular signal-regulated kinase-2) activity. CRP at acute phase levels increased both agonist-induced and noninduced phosphatidylinositol-3 kinase activity. The results suggest a role for CRP as a regulator of leukocyte infiltration at inflammatory sites.
Zhong
W
W
Department of Microbiology and Comprehensive Cancer Center, Ohio State University, Columbus 43210, USA.
Zen
Q
Q
Tebo
J
J
Schlottmann
K
K
Coggeshall
M
M
Mortensen
R F
RF
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000187:drug effects / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000276:immunology; D018922:HL-60 Cells; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D010446:Peptide Fragments / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011971:Receptors, Immunologic / Q000276:immunology; D018123:Receptors, Interleukin / Q000187:drug effects / Q000378:metabolism; D023062:Receptors, Interleukin-8A; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D002097:C-Reactive Protein; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D016209:Interleukin-8; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010446:Peptide Fragments; D019869:Phosphatidylinositol 3-Kinases; D011971:Receptors, Immunologic; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; C071581:CRP protein, human; C055978:N-formyl-methionyl-leucyl-phenylalanyl-phenylalanine