C-reactive protein inhibits intracellular calcium mobilization and superoxide production by guinea pig alveolar macrophages.
C-reactive protein (CRP) is a prototypical acute-phase reactant, the humoral and plasma concentrations of which rise dramatically after tissue injury or inflammation. The effects of CRP on superoxide production and intracellular calcium mobilization by guinea pig alveolar macrophages challenged with platelet-activating factor (PAF), N-formyl-methionyl-leucyl-phenylalanine (fMLP), and phorbol 12-myristate 13-acetate (PMA) were studied. CRP by itself did not activate alveolar macrophages up to a concentration of 100 micrograms/ml, whereas it inhibited superoxide production in a time- and dose-dependent manner with median inhibitory concentration (IC50) values of 4.2 +/- 0.3, 3.0 +/- 0.2, and 3.2 +/- 0.3 micrograms/ml for PAF (10(-7) M), fMLP (10(-7) M), and PMA (10(-9) M), respectively. When CRP was incubated with the agonists before addition to cells, it inhibited PMA-, PAF-, and to a lesser extent fMLP-induced superoxide production. CRP also attenuated the rise in intracellular free calcium levels evoked by fMLP or PAF in a dose-dependent manner. These findings suggest that CRP may play a role in attenuating tissue damage secondary to activation of alveolar macrophages by inhibiting superoxide generation and mobilization of intracellular free calcium.
Földes-Filep
E
E
Department of Pharmacology, Faculty of Medicine, University of Sherbrooke, Québec, Canada.
Filep
J G
JG
Sirois
P
P
D000818:Animals; D002097:C-Reactive Protein / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D010972:Platelet Activating Factor; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002097:C-Reactive Protein; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium