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.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.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.
Objectives To analyse the views of general practitioners (GPs) about how they can provide care to homeless people (HP) and to explore which measures could influence their views. Design Mixed-methods design (qualitative –> quantitative (cross-sectional observational) → qualitative). Qualitative data were collected through semistructured interviews and through questionnaires with closed questions. Quantitative data were analysed with descriptive statistical analyses on SPPS; a content analysis was applied on qualitative data. Setting Primary care; views of urban GPs working in a deprived area in Marseille were explored by questionnaires and/or semistructured interview. Participants 19 GPs involved in HP's healthcare were recruited for phase 1 (qualitative); for phase 2 (quantitative), 150 GPs who provide routine healthcare (‘standard’ GPs) were randomised, 144 met the inclusion criteria and 105 responded to the questionnaire; for phase 3 (qualitative), data were explored on 14 ‘standard’ GPs. Results In the quantitative phase, 79% of the 105 GPs already treated HP. Most of the difficulties they encountered while treating HP concerned social matters (mean level of perceived difficulties=3.95/5, IC 95 (3.74 to 4.17)), lack of medical information (mn=3.78/5, IC 95 (3.55 to 4.01)) patient's compliance (mn=3.67/5, IC 95 (3.45 to 3.89)), loneliness in practice (mn=3.45/5, IC 95 (3.18 to 3.72)) and time required for the doctor (mn=3.25, IC 95 (3 to 3.5)). From qualitative analysis we understood that maintaining a stable follow-up was a major condition for GPs to contribute effectively to the care of HP. Acting on health system organisation, developing a medical and psychosocial approach with closer relation with social workers and enhancing the collaboration between tailored and non-tailored programmes were also other key answers. Conclusions If we adapt the conditions of GPs practice, they could contribute to the improvement of HP's health. These results will enable the construction of a new model of primary care organisation aiming to improve access to healthcare for HP.
