Resistance of leishmanial phosphatases to inactivation by oxygen metabolites.
Leishmania donovani promastigotes produce large quantities of two distinct acid phosphatases; a tartrate-resistant enzyme is localized to the external surface of the plasma membrane, and a tartrate-sensitive enzyme is secreted into the growth medium. It was shown previously that preincubation of human neutrophils and macrophages with the tartrate-resistant phosphatase markedly reduced the ability of these host cells to produce superoxide anions in response to stimulation with the activator formyl-methionyl-leucyl-phenylalanine. The possibility that the cell surface acid phosphatase or the phosphatase that is secreted into the extracellular fluid might compromise other host cell functions, especially intracellular ones, depends on the ability of the enzyme to resist exposure to toxic oxygen metabolites (e.g., superoxide anion, hydrogen peroxide, hypochlorite) generated by phagocytic cells. In the present report, we show that both leishmanial acid phosphatases were relatively resistant to inactivation by oxygen metabolites. At pH 5.5, the activity of the tartrate-resistant phosphatase was reduced 50% by incubation for 1 h with each of the following: 30 mM O2-, 500 mM hydrogen peroxide, and 6 mM hypochlorite ion. These concentrations are many fold greater than the concentrations of these substances that are generated by stimulated polymorphonuclear phagocytes. The tartrate-sensitive acid phosphatase differed markedly from the tartrate-resistant phosphatase in that the former was essentially insensitive to even very high concentrations of superoxide anion and hydrogen peroxide. Furthermore, 50% inactivation of the tartrate-sensitive leishmanial phosphatase required exposure to 35 mM hypochlorite for 30 min. These results indicate that the catalytic potential of these two leishmanial acid phosphatases probably survives exposure to toxic oxygen metabolites generated by neutrophils and macrophages.
D000135:Acid Phosphatase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D006997:Hypochlorous Acid / Q000494:pharmacology*; D007893:Leishmania donovani / Q000201:enzymology*; D013481:Superoxides / Q000494:pharmacology*; D013644:Tartrates / Q000494:pharmacology
D013644:Tartrates; D013481:Superoxides; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D000135:Acid Phosphatase