Abrogation of DTH response and mitogenic lectin- and alloantigen-induced activation of lymphocytes by calcium inhibitors TMB-8 and BAPTA-AM.
In vitro treatment of mouse lymphocytes with an intracellular calcium chelator BAPTA-AM significantly decreased lectin Concanavalin-A (Con-A)-induced and mixed lymphocyte reaction (MLR) mediated, alloantigen-induced lymphocyte activation as indicated by decreased percentage of lymphoblasts among the BAPTA-treated lymphocytes. In vivo treatment of mice with intracellular Ca(2+) antagonist TMB-8 was found to substantially impair delayed type hypersensitivity (DTH; cell mediated immune) response, as indicated by decreased footpad swelling on tuberculin challenge of mice sensitized with BCG, after a single treatment with a low dose of 0.01mg of TMB-8 per mouse. Interestingly, a second injection of a higher dose of TMB-8 (0.1mg per mouse) resulted in very significant (p=0.001) abrogation of DTH as indicated by complete absence of swelling of foot pad after PPD challenge in BCG-primed treated mice. All mice in this group showed fully impaired DTH response. Lymphocytes of allosensitized mice gave a significantly higher (p<0.05) MLR response than the naïve mice. However, a single treatment of allosensitized mice with 0.1mg TMB-8 resulted into a lower MLR response, comparable in magnitude to that of untreated naïve mice.
Saxena
Hari Mohan
HM
Department of Veterinary Microbiology, College of Veterinary Science, Punjab Agricultural University, Ludhiana 141004, India. hmsaxena@yahoo.com
Dikshit
Madhu
M
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D003208:Concanavalin A; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009163:Mycobacterium bovis / Q000276:immunology; D014373:Tuberculin / Q000276:immunology
D002121:Calcium Channel Blockers; D002614:Chelating Agents; D014373:Tuberculin; D003208:Concanavalin A; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid