With the present study, the first evidence is provided that the increase of CD4+CD25 high T cells and FoxP3 transcripts is associated with operational tolerance in liver transplanted patients during IS withdrawal.

Sepsis is characterized by a systemic inflammatory response followed by immunosuppression of the host. Metabolic defects and mitochondrial failure are common in immunocompromised patients with sepsis. The NLRP3 inflammasome is important for establishing an inflammatory response after activation by the purinergic P2X7 receptor. Here, we study a cohort of individuals with intra-abdominal origin sepsis and show that patient monocytes have impaired NLRP3 activation by the P2X7 receptor. Furthermore, most sepsis-related deaths are among patients whose NLRP3 activation is profoundly altered. In monocytes from sepsis patients, the P2X7 receptor is associated with mitochondrial dysfunction. Furthermore, activation of the P2X7 receptor results in mitochondrial damage, which in turn inhibits NLRP3 activation by HIF-1α. We show that mortality increases in a mouse model of sepsis when the P2X7 receptor is activated in vivo. These data reveal a molecular mechanism initiated by the P2X7 receptor that contributes to NLRP3 impairment during infection.

SummaryImmune cells are equipped with a number of receptors that recognize sterile injury and pathogens. We find that host immune cells release ATP as an inflammatory signal in response to allogeneic transplantation. ATP then acts via a feedback mechanism on the P2X7 channel to activate the NLRP3 inflammasome and subsequently process and release interleukin (IL)-18. This process is a necessary stage in the deleterious Th1 response against allotransplantation via interferon-γ production. Lack of IL-18 resulted in a decrease in graft-infiltrating CD8 cells but an increase in regulatory T cells. In human liver transplant patients undergoing progressive immunosuppressive drug withdrawal, we found that patients experiencing acute rejection had higher levels of the P2X7 receptor in circulating inflammatory monocytes compared to tolerant patients. These data suggest that the pharmacological inhibition of the P2X7 receptor or the NLRP3 inflammasome will aid in inducing transplant tolerance without complete immunoparalysis.

Patients on the waiting list for a kidney transplant do not have a very favorable attitude toward receiving a related-living donor organ, although members of their family have offered them one of their organs. The profile of a patient who would accept a related-living donated kidney is a young, single person, without descendents, and with a high level of education.

A third of healthcare personnel from several hospitals are not in favor of xenotransplantation. It is necessary to provide more information about the matter, especially in hospitals where there is a preclinical xenotransplantation program or where there is access to one, such as in the hospitals in this study.

SummaryThe Latin American (LA) population has similarities with the Spanish population which makes its integration into Spanish society easier. Objective: to analyze the attitude toward organ donation among Latin American citizens residing in Spain, to determine the psychosocial variables which affect this attitude, and to examine the correlation between donation rates of LA citizens in Spain and in their countries of origin. A random sample of LA residents in Spain was taken and stratified according to the respondent's nationality (n = 1.314), in the year 2010. Attitude was assessed using a validated questionnaire (PCID-DTO Dr Rios). The survey was self-administered and completed anonymously. Statistical analysis: Student's t-test, the v 2 test, and logistic regression analysis. There was a 94% completion rate (n = 1.237). Attitude toward donation was favorable in 60% of cases (n = 745), 12% (n = 145) were against, and 28% (n = 347) were undecided. The following variables were associated with attitude toward donation: sex (P = 0.038), level of formal education (P < 0.001), country of origin (P = 0.002), attitude toward the donation of a family member's organs (P < 0.001), having discussed donation with the family (P < 0.001), carrying out prosocial activities (P = 0.025), attitude toward cremation of the body (P < 0.001), attitude toward burial of the body (P < 0.001), attitude toward having an autopsy carried out (P < 0.001), previous experience of the organ donation and transplantation process (P < 0.001), fear of mutilation after donation (P < 0.001), knowledge that the Church has a positive attitude toward organ donation and transplantation (P < 0.001), knowledge of one's partner's attitude toward organ donation (P < 0.001), and a belief that one might need a transplant in the future (P < 0.001). The donation rates in this population group in Spain are higher than those recorded in their countries of origin (55.76 vs. <10 pmp; P < 0.001). The attitude toward organ donation among LA citizens residing in Spain is slightly worse than that reported in the native Spanish population and is determined by many psychosocial factors. The donation rates of LA citizens in Spain are higher than those in their countries of origin.

Introduction: Recent immunological and transgenic advances are a promising alternative using limited materials of human origin for transplantation. However, it is essential to achieve social acceptance of this therapy.Objective: To analyze the attitude of nursing students from Spanish universities toward organ xenotransplantation (XTx) and to determine the factors affecting their attitude.Materials and methods: Type of study: A sociological, multicentre, and observational study. Study population: Nursing students enrolled in Spain (n = 28,000). Sample size:A sample of 10 566 students estimating a proportion of 76% (99% confidence and precision of ±1%), stratified by geographical area and year of study. Instrument of measurement: A validated questionnaire (PCID-XenoTx-RIOS) was handed out to every student in a compulsory session. This survey was self-administered and selfcompleted voluntarily and anonymously by each student in a period of 5-10 min.Statistical analysis: descriptive analysis, Student's t test, the chi-square test, and a logistic regression analysis.Results: A completion rate: 84% (n = 8913) was obtained. If the results of XTx were as good as in human donation, 74% (n = 6564) would be in favor and 22% (n = 1946) would have doubts. The following variables affected this attitude: age (P < 0.001); sex (P < 0.001); geographical location (P < 0.001); academic year of study (P < 0.001); attitude toward organ donation (P < 0.001); belief in the possibility of needing a transplant (P < 0.001); discussion of transplantation with one's family (P < 0.001) and friends (P < 0.001); and the opinion of one's partner (P < 0.001). The following variables persisted in the multivariate analysis: being a male (OR = 1.436; P < 0.001); geographical location (OR = 1.937; P < 0.001); an attitude in favor of donation (OR = 1.519; P < 0.001); belief in the possibility of needing a transplant (OR = 1.497; P = 0.036);and having spoken about the issue with family (OR = 1.351; P < 0.001) or friends (OR = 1.240; P = 0.001). Conclusions:The attitude of nursing students toward organ XTx is favorable and is associated with factors of general knowledge about organ donation and transplantation and social interaction. K E Y W O R D S attitude, knowledge, Organ xenotransplantation, student nurses 1 | INTRODUC TI ON Due to this organ shortage and the increase in the indications for transplantation, there are increasing numbers of patients on the waiting list with the mortality that this brings with it. 1 In the search for definitive solutions, there is continued research into xenotransplantation (XTx) in order to attempt to obtain an inexhaustible source of cells and organs. 2,3 Although clinical XTx is not a reality at present, in preclinical trials it has been possible to obtain a functioning pig-baboon model. 6 Therefore, in vital organs and in emergency situations, XTx could be used as a bridge while waiting for a human organ. 7,8

Tumor necrosis factor (TNF)-α is a major pro-inflammatory cytokine produced in response to toll-like receptor stimulation. TNF-α release is controlled by the activity of TNF-α converting enzyme (TACE) that cut membrane-bound TNF-α to shed its ectodomain as a soluble cytokine. The purinergic receptor P2X ligand-gated ion channel 7 (P2X7) is activated in response to elevated concentrations of extracellular ATP and induces different pro-inflammatory pathways in macrophages to establish an inflammatory response. P2X7 receptor promotes the activation of the inflammasome and the release of interleukin-1β, the production of inflammatory lipids, and the generation of reactive oxygen species. In this study, we analyzed the mechanism of P2X7 receptor responsible of TNF-α release after priming macrophages with LPS doses ≤100 ng/ml. We found that P2X7 receptor increases the extracellular activity of TACE through the release of the mature form of TACE in exosomes. This effect was blocked using P2X7 receptor inhibitors or in macrophages obtained from P2X7 receptor-deficient mice. Elevation of intracellular Ca2+ and p38 mitogen-activated protein kinase after P2X7 receptor activation were involved in the release of TACE, which was able to process TNF-α on nearby expressing cells. Finally, we observed an increase of TNF-α in the peritoneal lavage of mice treated with LPS and ATP. In conclusion, P2X7 receptor induces the release of TACE in exosomes to the extracellular compartment that could amplify the pro-inflammatory signal associated to this receptor. These results are important for the development of therapeutics targeting P2X7 receptor.