Regulatory effect of the level of free Ca2+ of the host cell on the capacity of Trypanosoma cruzi to invade and multiply intracellularly.
We studied whether modification of the free intracellular Ca2+ level of a mammalian host cell would affect its susceptibility to infection by Trypanosoma cruzi or its capacity to support trypomastigote-->amastigote transformation and amastigote replication. Pretreatment of rat heart myoblasts (RHM) with BAPTA.AM or Quin-2.AM, intracellular Ca2+ chelators, decreased the susceptibility of these cells to infection by untreated trypomastigotes. This was evidenced by a significant drop in both the percentage of infected RHM and the average number of organisms per 100 host cells relative to control values. Similar RHM treatment with the Ca2+ ionophore ionomycin had the opposite effects. The rate of trypomastigote-->amastigote transformation measured in RHM that had been treated with BAPTA.AM, Quin-2.AM, or ionomycin before and after, but not during co-culture with trypomastigotes was not significantly altered. The rate of intracellular amastigote multiplication measured in RHM exposed to the intracellular Ca2+ chelators only after virtually all of the internalized trypomastigotes had transformed into amastigotes was significantly decreased by incubation with BAPTA.AM or Quin-2.AM but was increased by ionomycin. None of the drug treatments affected RHM viability to any significant extent. These results suggest that T. cruzi relies on host cell Ca(2+)-dependent events, utilizes host cell free Ca2+ during invasion, or both, and highlight a requirement for an adequate free Ca2+ level for effective intracellular T. cruzi multiplication but not for trypomastigote-->amastigote transformation.
Schettino
P M
PM
Department of Microbiology, Michigan State University, East Lansing 48824, USA.
Majumder
S
S
Kierszenbaum
F
F
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005456:Fluorescent Dyes; D006321:Heart / Q000187:drug effects / Q000469:parasitology*; D007202:Indicators and Reagents; D015759:Ionomycin / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D014349:Trypanosoma cruzi / Q000502:physiology*
D000634:Aminoquinolines; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D004533:Egtazic Acid; D015759:Ionomycin; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; C035739:Quin2; D002118:Calcium