Le Forum, Vol. 44 #4

https://digitalcommons.library.umaine.edu/francoamericain_forum/1106/thumbnail.jp

L'hopital saint-nicolas du bruille (saint-andre) a tournai de sa fondation a sa mutation en cloitre (1230-1611). 2 v.

Thèse de doctorat -- Université catholique de Louvain, 197

THE NA (+)/H+ EXCHANGER NHE-1, A CRUCIAL CELLULAR INTEGRATOR CONTROLLED BY ITS MEMBRANE ENVIRONMENT

International audienc

Regulation of Na+/H+ exchanger 1 allosteric balance by its localization in cholesterol- and caveolin-rich membrane microdomains.

International audienceThe Na+/H+ exchanger 1, which plays an essential role in intracellular pH regulation in most tissues, is also known to be a key actor in both proliferative and apoptotic processes. Its activation by H+ is best described by the Monod-Wyman-Changeux model: the dimeric NHE-1 oscillates between a low and a high affinity conformation, the balance between the two forms being defined by the allosteric constant L(0). In this study, influence of cholesterol- and caveolin-rich microdomains on NHE-1 activity was examined by using cholesterol depleting agents, including methyl-beta-cyclodextrin (MBCD). These agents activated NHE-1 by modulating its L(0) parameter, which was reverted by cholesterol repletion. This activation was associated with NHE-1 relocation outside microdomains, and was distinct from NHE-1 mitogenic and hormonal stimulation; indeed MBCD and serum treatments were additive, and serum alone did not change NHE-1 localization. Besides, MBCD activated a serum-insensitive, constitutively active mutated NHE-1 ((625)KDKEEEIRK(635) into KNKQQQIRK). Finally, the membrane-dependent NHE-1 regulation occurred independently of Mitogen Activated Protein Kinases, especially Extracellular Regulated Kinase activation, although this kinase was activated by MBCD. In conclusion, localization of NHE-1 in membrane cholesterol- and caveolin-rich microdomains constitutes a novel physiological negative regulator of NHE-1 activity

The role of testicular fluid on blood plasma levels of FSH and LH in the ram (1)

International audienc

Seminal plasma inhibits Chlamydia trachomatis infection in vitro, and may have consequences on mucosal immunity

The authors would also like to thank Dr Frank Follmann (SSI, Danemark) for kindly providing the CT strain used for the in vitro infection of A2EN cells, Drs Luc de Chaisemartin (UMR 996, Hôpital Bichat, France) and Julien Lemaître (IDMIT department, CEA, France) for providing advice concerning the development of the neutrophil functional assays, Dr Agathe Subtil (Institut Pasteur, Cellular Biology of Microbial infection unit) for helpful discussion on CT infection and inhibition, Asmaa Tazi for her help and Nicole Tavares, Jean-François Meritet and Nadjet Benhaddou, service de Bactériologie-Virologie de l'Hôpital Cochin, APHP Centre for conducting the IgG anti-chlamydia assays. The authors thank all the patients who provided samples, AP-HP (Assistance Publique Hôpitaux de Paris) and clinical personnel for collecting the samples; the Clinical Core of the CRT (Center of Translational Science) of the Institut Pasteur for their help with biomedical regulatory aspects of the project, in particular Anaïs Perilhou.International audienceSeminal plasma (SP) is the main vector of C. trachomatis (CT) during heterosexual transmission from male to female. It has immunomodulatory properties and impacts the susceptibility to HIV-1 infection, but its role has not been explored during CT infection. In the female reproductive tract (FRT), CT infection induces cytokine production and neutrophil recruitment. The role of neutrophils during CT infection is partially described, they could be at the origin of the pathology observed during CT infection. During this study, we developed an experimental in vitro model to characterize the impact of CT infection and SP on endocervical epithelial cell immune response in the FRT. We also studied the impact of the epithelial cell response on neutrophil phenotype and functions. We showed that the production by epithelial cells of pro-inflammatory cytokines increased during CT infection. Moreover, the pool of SP as well as individuals SP inhibited CT infection in a dose-dependent manner. The pool of SP inhibited cytokine production in a dose-dependent manner. The pool of SP altered gene expression profiles of infected cells. The culture supernatants of cells infected or not with CT, in presence or not of the pool of SP, had an impact on neutrophil phenotype and functions: they affected markers of neutrophil maturation, activation and adhesion capacity, as well as the survival, ROS production and phagocytosis ability. This study proposes a novel approach to study the impact of the environment on the phenotype and functions of neutrophils in the FRT. It highlights the impact of the factors of the FRT environment, in particular SP and CT infection, on the mucosal inflammation and the need to take into account the SP component while studying sexually transmitted infections during heterosexual transmission from male to female