Stimulation of phosphatidylethanolamine synthesis during the last stages of the G1 phase in concanavalin A-activated human peripheral lymphocytes

Author(s):  
Claude Rampini ◽  
Catherine Dubois

1999 ◽  
Vol 96 (1) ◽  
pp. 99-103 ◽  
Author(s):  
Moacir WAJNER ◽  
Kátia D. SANTOS ◽  
Jeanine L. SCHLOTTFELDT ◽  
Maureen P. ROCHA ◽  
Clóvis M. D. WANNMACHER

Recurrent infections are common features in patients affected by propionic acidaemia (McKusick 232000) and methylmalonic acidaemia (McKusick 251000). Since these disorders are biochemically characterized by tissue accumulation of propionic acid and methylmalonic acid respectively, it is possible that these compounds may act as immunosuppressants. We therefore investigated the effect of propionate and methylmalonate on cellular growth of human peripheral lymphocytes stimulated in vitro by phytohaemagglutinin, concanavalin A and pokeweed mitogen, a recognized test of cellular immunocompetence. Lymphocytes were cultured in flat-bottomed 96-well microplates at 37 ;°C for 96 ;h (phytohaemagglutinin and concanavalin A) or 144 ;h (pokeweed mitogen) in the presence of one mitogen at different concentrations and of one acid added at doses of 1.0, 2.5 or 5.0 ;mM. Cell blastogenesis was measured by the incorporation of tritiated thymidine into cellular DNA and compared with that of identical cultures with no acid added (controls). A consistent and progressive inhibitory effect of propionic acid with increasing concentrations in culture was identified with all mitogens and was more pronounced with pokeweed mitogen. Lymphocyte blastogenesis was not altered in the presence of methylmalonic acid. The effect of propionate was observed only when the drug was added at the beginning (phytohaemagglutinin-activated) or until 24 ;h (concanavalin A- and pokeweed mitogen-activated) of culture. The viability of lymphocytes after treatment with the drug, as assessed by the Trypan Blue exclusion test, revealed no change when compared with the same untreated lymphocytes, indicating no lymphocytotoxic activity. In conclusion, propionic acid, which accumulates in tissues of patients with propionic acidaemia, causes ‘in vitro’ immunosuppression, which may be related to the recurrent infections characteristic of these patients.



Blood ◽  
2010 ◽  
Vol 115 (21) ◽  
pp. 4185-4190 ◽  
Author(s):  
Nicholas J. Megjugorac ◽  
Grant E. Gallagher ◽  
Grant Gallagher

The type-III interferon (IFN) family is composed of 3 molecules in humans: IFN-λ1 (interleukin-29 [IL-29]), IFN-λ2 (IL-28A), and IFN-λ3 (IL-28B), each of which signals through the same receptor complex. Plasmacytoid dendritic cells (pDCs) are major IFN-λ producers among peripheral lymphocytes. Recently, it has been shown that IFN-λ1 exerts a powerful inhibitory effect over the T-helper 2 (Th2) response by antagonizing the effect of IL-4 on CD4+ T cells and inhibiting the production of Th2-associated cytokines. Here, we asked whether Th2 cytokines exert reciprocal control over IFN-λ production. IL-4 treatment during stimulation of human peripheral lymphocytes significantly elevated IFN-λ1 transcription and secretion. However, pDCs were not directly responsive to IL-4. Using depletion and reconstitution experiments, we showed that IL-4–responsive monocytes are an intermediary cell, responding to IL-4 by elevating their secretion of IL-1 receptor antagonist (IL-Ra); this IL-1Ra acts on pDCs to elevate their IFN-λ1 output. Thus, our experiments revealed a novel mechanism for regulation of both IFN-λ1 production and pDC function, and suggests an expanded immunomodulatory role for Th2-associated cytokines.



1990 ◽  
Vol 19 (2) ◽  
pp. 87-91 ◽  
Author(s):  
F.H. Hucklebridge ◽  
B.N. Hudspith ◽  
P.M. Lydyard ◽  
J. Brostoff


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