RESUMO
The inflammatory response is a key mechanism for the elimination of injurious agents but must be tightly controlled to prevent additional tissue damage and progression to persistent inflammation. C-type lectin receptors expressed mostly by myeloid cells play a crucial role in the regulation of inflammation by recognizing molecular patterns released by injured tissues. We recently showed that the C-type lectin receptor CLEC-1 is able to recognize necrotic cells. However, its role in the acute inflammatory response following tissue damage had not yet been investigated. We show in this study, in a mouse model of liver injury induced by acetaminophen intoxication, that Clec1a deficiency enhances the acute immune response with increased expression of Il1b, Tnfa, and Cxcl2 and higher infiltration of activated neutrophils into the injured organ. Furthermore, we demonstrate that Clec1a deficiency exacerbates tissue damage via CXCL2-dependent neutrophil infiltration. In contrast, we observed that the lack of CLEC-1 limits CCL2 expression and the accumulation, beyond the peak of injury, of monocyte-derived macrophages. Mechanistically, we found that Clec1a-deficient dendritic cells increase the expression of Il1b, Tnfa, and Cxcl2 in response to necrotic cells, but decrease the expression of Ccl2. Interestingly, treatment with an anti-human CLEC-1 antagonist mAb recapitulates the exacerbation of acute immunopathology observed by genetic loss of Clec1a in a preclinical humanized mouse model. To conclude, our results demonstrate that CLEC-1 is a death receptor limiting the acute inflammatory response following injury and represents a therapeutic target to modulate immunity.
Assuntos
Inflamação , Neutrófilos , Camundongos , Animais , Células Mieloides , Macrófagos , Fígado/metabolismo , Lectinas Tipo C/metabolismoRESUMO
PURPOSE: To evaluate the performance of a 'one-stop' clinic in terms of proportion of discharges or inclusion in surgical waiting lists. MATERIALS AND METHODS: All patients were referred from primary care facilities (population 220.646) and from different departments in the hospital. Eight senior urologists, two registered nurses and two nurse attendants participated in the experience. Prior to the start of the project, referral protocols had been agreed with the primary care physicians involved. Compliance with the protocols was periodically tested. Eventually 5537 first visits (January-December 2009) where evaluable. RESULTS: Overall, the 'one-stop' format proved feasible in 74.2 percent of the patients (4108/5537). Patients, who successfully used the 'one-stop' format, were significantly younger than those who required additional consultations (43 vs 50 years old, respectively, Student's t test < 0.001). For obvious reasons the 'one-stop' format was universally possible in male sterilization and penile phimosis patients. Similarly, the 'one-stop' policy was applied in most consultations due to male sexual dysfunction (75 percent) and urinary tract infection (73 percent). Other health problems, such as haematuria (62 percent) and renal colic (46 percent), required more than one visit so that care of the patient reverted to the traditional, outpatient care model. CONCLUSION: A 'one-stop' philosophy is feasible for a number of procedures in a urological outpatient clinic. The costs to implement such an approach would be limited to managerial expenditure.