Nitric Oxide-Induced Lymphocyte Activation: A Role for G Proteins

Abstract

Oxygen free radical generation has been implicated in mediating signal transmission initiated by a variety of stimuli (1–4). For example, Novogrodsky et al. (2) discovered that hydroxy radical scavengers blocked phorbol ester-induced mitogenesis in lymphocytes. Also, Schreck et al. (1) found that treating T lymphocytes with the free radical scavenger N-acetylcysteine, blocked activation of the nuclear transcription factor NF-κB by a variety of unrelated stimuli. We discovered various inductive effects which oxidants and other stress stimuli, such as Hg²⁺ and phenylarsine oxide, have on resting human peripheral blood mononuclear cells (PBMC) (5–9). We examined early parameters of cellular activation, including the rate of glucose uptake, p56^lck protein tyrosine kinase activity and CD45 protein tyrosine phosphatase activity. The ability of hemin, Hg²⁺ and phenylarsine oxide to activate this signal transduction pathway led us to examine whether a more biologically relevant oxidant, nitric oxide, had similar effects (10).