Cyclic nucleotide changes induced in human leukocytes by a product of axenically grown Entamoeba histolytica that inhibits human monocyte locomotion.

Pulse exposure of human mononuclear phagocytes to the monocyte locomotion-inhibitory factor produced by Entamoeba histolytica (i.e., the 369- to 765-Da chromatographic fraction obtained from the supernatant fluid of axenically grown E. histolytica) led to a swift increase in the intracellular concentration of adenosine 3':5' cyclic monophosphate (cAMP). A weaker response was observed in human polymorphonuclear leukocytes, the locomotion of which, however, is not inhibited by this amebic factor. The same chromatographic fraction obtained from the axenic medium control lacked this effect, at least upon mononuclear phagocytes. On the other hand, both the monocyte locomotion-inhibitory factor and the axenic medium control, possibly through shared cultured medium components, induced comparable increases in guanosine 3':5' cyclic monophosphate (cGMP) in human mononuclear phagocytes and in polymorphonuclear leukocytes, thus suggesting that the latter-nucleotide is not critical for the leukotactic inhibitory phenomenon. Our results suggest that like other leukotactic inhibitors, the monocyte locomotion-inhibitory factor produced by E. histolytica operates through modulations of intracellular cAMP.