Éditeur(s) : HAL CCSD
Résumé : International audience
Objective Macrophages may play a significant role in the initiating stages leading to chronic inflammation/infection in cystic fibrosis (CF), via an inability to act as a suppressor cell. In a previous study demonstrating impaired function of CF macrophage, we have shown high production of soluble CD14 (sCD14). The aim of the present work is to determine origin and function of sCD14 in blood monocyte-derived macrophages from stable adult CF patients. Methods To study origin, sCD14 is measured by ELISA in supernatant of macrophages from healthy subjects (non-CF) treated with PI-PLC or cholesterol. The involvement of sCD14 in inflammation, was investigated by analysis of NF-kB and caspase 1 pathways in non-CF macrophages treated by sCD14. Measurement of gene expression was done by qPCR and proteins were quantified by ELISA and Western blot. Results Treatment with PI-PLC increased sCD14 level in the supernatant of non-CF macrophages whereas cholesterol did not modified it. Furthermore high secretion of sCD14 from CF macrophages was decreased by an inhibitor of PI-PLC. Treatment with sCD14 increased pro-IL-1β, IL-8 and TNF-α expression resulting from NF-kB activation through IkBa phosphorylation, this effect was inhibited by NF-kB inhibitors. Also, activation of caspase 1 by cleavage of pro-caspase 1 allowed the secretion of mature IL-1β, inhibited by an inhibitor of caspase 1. However, inflammasome complex involved in caspase 1 activation remains to be determined. Conclusion This data show that origin of sCD14 is partly due to the action of lipases cutting the GPI tail that serves as a membrane anchor to CD14. Furthermore sCD14 have a role in chronic inflammation in CF
the 38th European Cystic Fibrosis Conference
Vienne, Austria

hal-01162773
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01162773
DOI : 10.1016/S1569-1993(15)30203-4

Éditeur(s) : HAL CCSD
Résumé : International audience
Objective Oxidative stress, excess production of reactive oxygen species (ROS) and intense colonization of the respiratory tract by microorganisms are described in CF patients, leading to an influx in macrophages. This results in activation of NADPH oxidase that yields ROS, initiating the oxidative burst responsible for pathogen destruction. We showed that phagocytosis was altered in CF macrophages, yet oxidative status in this cell was not defined. The objective of this study is to draw a link between oxidative stress and plasma membrane integrity in CF macrophages, since lipid peroxidation is known to alter cell membrane. Methods Peripheral blood monocytes-derived macrophages were obtained from CF patients and healthy subjects. Plasma membrane fluidity was assessed with di4-ANEPPDHQ and oxidative status was measured with ROS indicating probes. Results In CF macrophages, membrane fluidity was increased whereas lipid peroxidation was diminished. Surprisingly, general oxidative status remained similar to the one observed in non-CF macrophages. Also, CF macrophages did not abolish chemically induced-oxidative stress. In non-CF macrophages, treatment with cholesterol slightly increased membrane fluidity whereas LPS treatment had no effect. Conclusion CF macrophages displayed an increased membrane fluidity associated with a decreased lipid peroxidation. This raises the hypothesis that membrane alteration in CF macrophages may be due to other mechanism than oxidative stress. Nevertheless, since the killing capacity of CF macrophage is defective, a deregulation of O•−2 production is very likely, suggesting alteration of NADPH oxidase or mitochondrial dysfunction
the 38th European Cystic Fibrosis Conference
Vienne, Austria

hal-01162769
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01162769
DOI : 10.1016/S1569-1993(15)30217-4

Éditeur(s) : HAL CCSD
Résumé : International audience
Objectives: To assess the adhesion of French obstetricians and gynecologists to the French clinical practice guidelines for pregnancy loss, issued by the French College of Obstetricians and Gynecologists, one year after publication.Methods: An online vignette-based study was emailed to a sample of French obstetricians and gynecologists to compare their management of women with missed early miscarriage and incomplete early miscarriage. A descriptive statistical analysis was performed comparing the rates of appropriate management for these two indications before and after the release of the guidelines.Results: Of the 404 specialists contacted, 143 completed the questionnaire. Forty-three percent stated that they had changed their practices following the release of the guidelines. The rate of adhesion was moderate for the management of missed early miscarriage (53% after publication of the guidelines versus 42% before, P = 0.001) with a trend to avoid watching-and-waiting management. The rate of adhesion was poor for the management of incomplete early miscarriage (43% after the publication of the guidelines versus 27% before, P < 0.001) with a lower use of misoprostol.Conclusion: Adhesion to the French guidelines appears to be moderate for the management of missed early miscarriage and low for the management of incomplete early miscarriage.
ISSN: 24687847

hal-01558814
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01558814
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01558814/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01558814/file/Le%20Gouic%20et%20al.%20-%20Evaluation%20of%20adherence%20to%20French%20clinical%20practic.pdf
DOI : 10.1016/j.jogoh.2017.03.005