Splenocyte glutathione and CD3-mediated cell proliferation are reduced in mice fed a protein-deficient diet.

Protein-energy malnutrition (PEM) is associated with decreased host immune defense. Glutathione (GSH) status is reported to be decreased in PEM, and GSH is important for lymphocyte function. The objective of the present study was to investigate the effects of PEM and dietary repletion (RP) on GSH status in various tissues and splenocytes and on CD3-mediated calcium mobilization and cell proliferation of splenic T-lymphocytes. For the PEM model, mice were fed a 0.5% protein diet (LP group) for 4 or 6 wk, and control mice were fed a 15% protein diet (CP group). In the RP study, LP mice were fed the 15% protein diet for 3 d, 1 wk, 2 wk or 3 wk (RP groups). Glutathione concentrations were significantly lower in liver, lung, heart and spleen of LP mice compared with CP mice at 4 and 6 wk. Splenocytes from LP mice were significantly lower in number and had a lower intracellular GSH concentration, depressed CD3-stimulated T-lymphocyte proliferation in culture media without thiol supplementation (2-mercaptoethanol), and enhanced CD3-stimulated proliferation in thiol-supplemented culture media compared with splenocytes from CP mice. CD3-stimulated calcium mobilization was significantly lower in CD8+, but not CD4+, splenocytes from LP mice. Within 1 wk of dietary repletion, splenocyte GSH concentration was normal and splenocyte numbers were greater, and in vitro sensitivity of CD3-stimulated T-lymphocyte proliferation to thiol was lower, compared with LP mice. Glutathione status in vivo and thiol supplementation in vitro seem to modulate the signal transduction pathway for T-lymphocyte proliferation in mice with PEM.

The effect of in vitro phorone exposure on glutathione content and T cell antigen receptor (CD3)-stimulated calcium mobilization in murine splenic T lymphocytes.

An increase in cytosolic free calcium ([Ca(2+)](i)) is one of the earliest events to occur in T lymphocytes following stimulation of the transmembrane T cell receptor/CD3 complex (TCR/CD3). This [Ca(2+)](i) mobilization has been found to be sensitive to intracellular thiol redox status, which in turn is modulated by cellular glutathione (GSH) content. We have previously reported that GSH depletion, by treatment with either the alpha, beta-carbonyl diethyl maleate or the aromatic halo-compound 1-chloro-2,4-dinitrobenzene, correlates with decreased [Ca(2+)](i) mobilization in anti-CD3 monoclonal antibody (mAb)-stimulated human peripheral blood lymphocytes (HPBL). This prompted us to determine whether this correlation between GSH content and TCR/CD3 signal transduction capability was also present in murine lymphocytes, since the mouse model is often used as a surrogate for the human immune system. The results presented here demonstrate that in vitro treatment with the alpha, beta-carbonyl phorone dose-dependently depletes intracellular GSH in murine splenic T lymphocytes. Both CD4(+) and CD8(+) T lymphocytes depleted of GSH by greater than 40% were found to have a decreased [Ca(2+)](i) mobilization following anti-CD3 mAb stimulation. Similar to what has been described for HPBL, these results indicate that the cellular GSH status influences the initial response of murine T lymphocytes to TCR/CD3 stimulation.

Potassium-stimulated efflux of radiolabeled products formed from L-[14C(U)]-glutamine in vitro by the saccule of the rainbow trout (Salmo gairdnerii R.).

Samples of saccular macula from the rainbow trout were incubated in vitro with uniformly-labeled L-[14C]-glutamine, and radiolabeled products, released by potassium-induced depolarization in the presence of calcium, were examined. Most of the effluxed radioactivity was distributed in six (of 17) thin-layer chromatographic fractions. Fractions corresponding to aspartate and glutamate showed highly significant increases in radioactivity (as percent of total recovered radioactivity) during high-potassium treatment. Radioactivity in a fraction with an RF close to that of ornithine also significantly increased during potassium, and dropped sharply after potassium. The origins of the thin-layer fractions, with respect to sensory and neural elements in the saccular macula samples, are discussed.

Intranasal glomus tumor.

The glomus tumor, or glomangioma, is a hyperplastic or hamartomatous lesion of the glomus body. It is composed of vascular channels surrounded by characteristic "epithelioid" cells, which are probably derived from smooth muscle. Glomus tumors rarely occur in the head and neck. We encountered the fifth documented case, to our knowledge, of a glomus tumor presenting in the nasal cavity. Although the lesion in this case was asymptomatic, intranasal glomus tumors producing nasal obstruction, pain, and epistaxis have been described. The complete excision of a glomus tumor normally cures the condition.