Effect of antagonists of calcium and phospholipase A on the cytopathogenicity of Entamoeba histolytica.
The in vitro mechanisms by which Entamoeba histolytica trophozoites lyse target Chinese hamster ovary (CHO) cells were examined. Calcium chelators ethylenediaminetetraacetate and ethyleneglycol bis (beta-aminoethyl ether)-N,N'-tetraacetate (10 mM) inhibited amebic cytolysis of target CHO cells (P less than .01). A putative antagonist of intracellular calcium flux, 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8; greater than or equal to 250 microM), inhibited amebic adherence and cytolysis (P less than .001). Quinacrine, Rosenthal's inhibitor (dimethyl-dl-2,3-distearoyloxypropyl-2'-hydroxyethyl ammonium acetate), phosphatidylcholine, and hydrocortisone (greater than or equal to 10(-4) M), all pharmacological antagonists of eukaryotic phospholipase A enzymes, inhibited amebic killing of target CHO cells (P less than .001). At 37 C quinacrine and hydrocortisone reduced amebic adherence to CHO cells, whereas Rosenthal's inhibitor and phosphatidylcholine did not. Phosphatidylcholine and TMB-8 demonstrated a synergistic inhibitory effect on amebic killing of target CHO cells (P less than .001). These studies indicate that extracellular calcium ions, amebic intracellular calcium flux, and amebic phospholipase A activity are required for cytolysis of target cells by E. histolytica.
Ravdin
J I
JI
Murphy
C F
CF
Guerrant
R L
RL
Long-Krug
S A
SA
D000268:Adhesiveness; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival; D006224:Cricetinae; D004492:Edetic Acid / Q000494:pharmacology; D004748:Entamoeba histolytica / Q000201:enzymology / Q000378:metabolism / Q000472:pathogenicity*; D005260:Female; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology; D010053:Ovary; D010713:Phosphatidylcholines / Q000494:pharmacology; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011796:Quinacrine / Q000494:pharmacology; D013228:Stearates / Q000494:pharmacology
D002121:Calcium Channel Blockers; D010713:Phosphatidylcholines; D013228:Stearates; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; C015161:Rosenthal's inhibitor; D004492:Edetic Acid; D010740:Phospholipases; D010741:Phospholipases A; D011796:Quinacrine; D002118:Calcium; D006854:Hydrocortisone