Obligatory role of Ca2+ in the cytotoxic activity of dengue virus-induced cytotoxin.
The role of calcium ions (Ca2+) in the cytotoxic activity of the dengue type 2 virus (DV)-induced macrophage (M phi) cytotoxin (CF2) was investigated in the present study. The findings show that CF2 prepared in Ca(2+)-free medium had no cytotoxic activity on normal mouse spleen cells suspended in Ca(2+)-free medium but killed the cells suspended in the medium with Ca2+. Substitution with calcium chloride restored the cytotoxic activity of CF2 the optimal dose being 10(-4) M concentration. CF2 induced an influx of Ca2+, as assayed by uptake of radiolabelled calcium chloride (45Ca), in the susceptible target cells, viz. M phi and T lymphocytes. The cytotoxic activity of CF2 as well as the CF2-induced influx of 45Ca was inhibited by treatment of the target cell with the calcium channel blocking drugs verapamil and nifedipine. Thus, the presence of Ca2+ is obligatory for the cytotoxic activity of CF2 and cell death is associated with increased intracellular Ca2+.
Dhawan
R
R
Postgraduate Department of Microbiology, K.G. Medical College, Lucknow, India.
Chaturvedi
U C
UC
Khanna
M
M
Mathur
A
A
Tekwani
B L
BL
Pandey
V C
VC
Rai
R N
RN
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D002470:Cell Survival; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003603:Cytotoxins / Q000378:metabolism*; D003715:Dengue / Q000276:immunology* / Q000378:metabolism; D003716:Dengue Virus / Q000276:immunology*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D013154:Spleen / Q000166:cytology; D014759:Viral Envelope Proteins / Q000378:metabolism*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D003603:Cytotoxins; C051821:E-glycoprotein, Dengue virus type 2; D014759:Viral Envelope Proteins; D002118:Calcium