The requirement of serine esterase function in complement-dependent erythrophagocytosis.
The p-nitrophenyl ethyl phosphonate esters have been shown to inhibit complement-dependent erythrophagocytosis when exposed to guinea pig polymorphonuclear leukocytes prior to the initiation of phagocytosis. Inhibition of phagocytosis occurred in a manner characteristic of the well-defined capacity of phosphonate esters to inactivate serine esterases: inhibition was irreversible, dependent upon the temperature of reaction and pH of the reaction medium, and proportional to the concentration of inhibitor used and the duration of exposure between leukocytes and inhibitor. Phosphonate inhibition was further shown to be independent of any general cell damaging effects of the compounds used. The phagocytic enzyme inhibited by phosphonate esters apparently exists in or on leukocytes in an already activated state prior to the initiation of the phagocytic process. The inhibitory profile of the activated phagocytic esterase was found to be essentially identical to the profile of inhibition previously obtained for the activated chemotactic esterase of rabbit polymorphonuclear leukocytes, suggesting that the same enzyme may function in both chemotaxis and phagocytosis. Various substrates including acetate esters reported to protect the activated chemotactic esterase from inhibition by phosphonate esters did not exhibit a clear protective effect in the phagocytic system and attempts to define the relationship between the two enzymes were unsuccessful. Suggestive evidence was also obtained for the requirement of the function of a second, activatable esterase in the phagocytic process.
D000818:Animals; D002633:Chemotaxis / Q000187:drug effects; D003165:Complement System Proteins; D004789:Enzyme Activation; D004950:Esterases / Q000037:antagonists & inhibitors*; D004952:Esters / Q000494:pharmacology; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D007962:Leukocytes / Q000201:enzymology; D063065:Organophosphonates / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects*; D012694:Serine; D013696:Temperature
D004952:Esters; D063065:Organophosphonates; D012694:Serine; D003165:Complement System Proteins; D004950:Esterases