Calcium channel antagonist (nifedipine) attenuates Plasmodium berghei-specific T cell immune responses in Balb/C mice.
Nifedipine and verapamil (Martin et al. Science 1987;235:899-901) are a class of calcium channel blockers involved in the reversal of chloroquine (CQ) drug resistance in CQ-sensitive Plasmodium spp. Nifedipine alters calcium-dependent functions of macrophages and neutrophils during Plasmodium berghei malaria. However, knowledge of nifedipine-induced immunomodulation of T cell functions during P. berghei malaria is still limited. We investigated the effect of nifedipine on the immune status of splenic T cells during P. berghei malaria. The intracellular calcium levels were determined in the FURA-2A/M loaded T cells by spectrofluorometry. Splenic T cell proliferation, phosphatidylserine (PS) externalization, Fas expression and Bcl2/Bax expression were determined by flow cytometry. We report a significant increase in mean percent parasitemia in nifedipine-treated and P. berghei-infected mice. Although nifedipine treatment alone did not affect the resting state free calcium levels in splenic T cells, the rise in intracellular calcium levels of T cells following P. berghei infection was significantly less in nifedipine-treated mice compared to untreated groups at various parasitemia levels. Antigen-specific splenic T cell proliferation and apoptosis was ablated in nifedipine-treated and untreated groups at various parasitemia levels. The study unequivocally reflects the suppression of P. berghei-specific T cell immune responses by nifedipine.
Moshal
Karni S
KS
B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India.
Adhikari
Jawahar S
JS
Bist
Kamana
K
Nair
Unnikrishnan
U
Dwarakanath
B S
BS
Katyal
Anju
A
Chandra
Ramesh
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005260:Female; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009543:Nifedipine / Q000494:pharmacology*; D010962:Plasmodium berghei / Q000276:immunology*; D013163:Splenomegaly / Q000517:prevention & control; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D019014:fas Receptor / Q000032:analysis
D002121:Calcium Channel Blockers; D019014:fas Receptor; D009543:Nifedipine; D002118:Calcium