Fractalkine Expression Induces Endothelial Progenitor Cell Lysis by Natural Killer Cells

BACKGROUND: Circulating CD34(+) cells, a population that includes endothelial progenitors, participate in the maintenance of endothelial integrity. Better understanding of the mechanisms that regulate their survival is crucial to improve their regenerative activity in cardiovascular and renal diseases. Chemokine-receptor cross talk is critical in regulating cell homeostasis. We hypothesized that cell surface expression of the chemokine fractalkine (FKN) could target progenitor cell injury by Natural Killer (NK) cells, thereby limiting their availability for vascular repair. METHODOLOGY/PRINCIPAL FINDINGS: We show that CD34(+)-derived Endothelial Colony Forming Cells (ECFC) can express FKN in response to TNF-α and IFN-γ inflammatory cytokines and that FKN expression by ECFC stimulates NK cell adhesion, NK cell-mediated ECFC lysis and microparticles release in vitro. The specific involvement of membrane FKN in these processes was demonstrated using FKN-transfected ECFC and anti-FKN blocking antibody. FKN expression was also evidenced on circulating CD34(+) progenitor cells and was detected at higher frequency in kidney transplant recipients, when compared to healthy controls. The proportion of CD34(+) cells expressing FKN was identified as an independent variable inversely correlated to CD34(+) progenitor cell count. We further showed that treatment of CD34(+) circulating cells isolated from adult blood donors with transplant serum or TNF-α/IFN-γ can induce FKN expression. CONCLUSIONS: Our data highlights a novel mechanism by which FKN expression on CD34(+) progenitor cells may target their NK cell mediated killing and participate to their immune depletion in transplant recipients. Considering the numerous diseased contexts shown to promote FKN expression, our data identify FKN as a hallmark of altered progenitor cell homeostasis with potential implications in better evaluation of vascular repair in patients

"Louis François et les frontières scolaires (1904-2001)"

National audienc

Associations between Thyroid Stimulating Hormone Levels and Both Severity and Early Outcome of Patients with Ischemic Stroke

International audienceWe aimed to investigate associations between serum thyroid stimulating hormone (TSH) levels and both severity and outcome after ischemic stroke (IS). A total of 731 patients consecutive IS patients were enrolled (mean age 69.4 +/- 15.4, 61.6% men), and serum TSH levels were measured at admission and analyzed according to the tertiles of their distribution (1.6 mUI/l). Associations between TSH and both severity at admission (National Institutes of Health Stroke Scale (NIHSS) scores = 5) and functional outcome at discharge assessed by the modified Rankin Scale were analyzed using logistic regression and ordinal logistic regression models, respectively. High TSH levels were independently associated with both a decreased risk of NIHSS score >= 5 at admission (prevalence proportion ratio = 0.62; 95% CI 0.41-0.94, p = 0.024 for tertile 3 vs. tertile 1). In addition, patients with high TSH levels had a better functional outcome at discharge (OR 0.43; 95% CI 0.30-0.60, p < 0.001 for tertile 2 vs. tertile 1; OR 0.39; 95% CI 0.27-0.56, p < 0.001 for tertile 3 vs. tertile 1). The mechanisms underlying these associations and their potential exploitation in terms of therapeutic strategies need to be explored

Association between Admission Serum 25-Hydroxyvitamin D Levels and Functional Outcome of Thrombolyzed Stroke Patients

International audienceBackground: 25-Hydroxyvitamin D (25(OH)D) deficiency is a frequent condition in patients who suffer a stroke, and several studies suggested that it may be associated with a poorer prognosis. The aim of this study was to investigate specifically the association between 25(OH)D levels and functional outcome at 3 months in ischemic stroke patients treated with intravenous thrombolysis. Methods: Consecutive ischemic stroke patients who received intravenous thrombolysis were enrolled between 2010 and 2013. Baseline characteristics were collected, and serum concentrations of 25(OH)D were measured within the first 24 hours after admission and were analyzed according to the quartiles of their distribution (= 25 nmol/L). Multivariable ordinal logistic regression was used to evaluate the association between 25(OH)D and 3-month functional outcome assessed by the modified Rankin score. Results: Three hundred fifty-two patients were included (mean age 68.6 +/- 15.8, 50.7% women, mean 25(OH)D level 45 +/- 25 nmol/L). The characteristics of the patients only differed with regard to higher premorbid functional impairment in patients with low 25(OH)D. In univariate analysis, the risk of functional impairment in patients with low 25(OH)D levels was greater than that in patients with higher 25(OH) D levels (odds ratio [OR] 2.10, 95% confidence interval [CI]: 1.35-3.27, P = .001). This association was still observed after adjustment for confounding variables (OR 1.70, 95% CI: 1.06-2.71, P = .027). Conclusion: A low serum 25(OH)D level is associated with worse functional outcome in patients with acute ischemic stroke treated with intravenous thrombolysis. Further investigations are required to understand the underlying mechanisms of this association

Recurrent cystitis episodes are caused by "ordinary" uropathogenic Escherichia coli strains

Recurrent cystitis (i.e. more than 2 episodes over a 6-month period) is a public health concern as it impacts significantly the patients' quality of life. Both sporadic cystitis (SC) and recurrent cystitis (RC) are mainly caused by Uropathogenic Escherichia coli (UPEC). However, specific determinants associated with "recurrent" UPEC remain poorly characterized. → Objective: to describe genomic and phenotypic traits associated with recurrence and to explore within host genomic adaptation of sequential UPEC isolates