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Amphotericin B both inhibits and enhances T-cell proliferation: Inhibitory effect is mediated through H2O2 production via cyclooxygenase pathway by macrophages by Sanjeev Kumar; Rabindranath Chakrabarti is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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Amphotericin B (AmB) has been shown to have both immunosuppressive and -enhancing effects, making its precise nature of action enigmatic. In the present study, we found that AmB inhibited concanavalin A (Con A)-induced T cell proliferation if added within first 30 min of stimulation, after which inhibition began to diminish rapidly. However, AmB did not inhibit T-cell proliferation induced by a combination of PMA and ionomycin. AmB inhibition of Con A-induced proliferation was completely overcome by cyclooxygenase inhibitor ibuprofen ([␣-methyl-4-(isobutyl)phenylacetic acid]) and H 2 O 2 scavenger catalase. In fact, in the presence of ibuprofen and catalase, AmB enhanced, instead of suppressing, Con A-induced proliferation in a dose-dependent way. The effect of catalase was limited to the removal of extracellular H 2 O 2 only, as the enzyme did not enter the cells. AmB stimulated H 2 O 2 production by macrophages, but not by a lymphocyte population, which was inhibited by ibuprofen. Our T-cell preparation contained about 3% macrophages, and AmB inhibition of proliferation was further pronounced by increasing the macrophage number by as little as 1%. Finally, AmB inhibition of Con A

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Author

Sanjeev Kumar; Rabindranath Chakrabarti

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley (ISSN 0730-2312)

Published

2000

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)