RESUMEN
Pseudomonas aeruginosa is a key opportunistic pathogen causing disease in cystic fibrosis (CF) and other lung diseases such as chronic obstructive pulmonary disease (COPD). However, the pulmonary host defense mechanisms regulating anti-P. aeruginosa immunity remain incompletely understood. Here we demonstrate, by studying an airway P. aeruginosa infection model, in vivo bioluminescence imaging, neutrophil effector responses and human airway samples, that the chemokine receptor CXCR1 regulates pulmonary host defense against P. aeruginosa. Mechanistically, CXCR1 regulates anti-Pseudomonas neutrophil responses through modulation of reactive oxygen species and interference with Toll-like receptor 5 expression. These studies define CXCR1 as a novel, noncanonical chemokine receptor that regulates pulmonary anti-Pseudomonas host defense with broad implications for CF, COPD and other infectious lung diseases.
Asunto(s)
Fibrosis Quística/inmunología , Neutrófilos/inmunología , Infecciones por Pseudomonas/inmunología , Pseudomonas aeruginosa/inmunología , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Receptores de Interleucina-8A/metabolismo , Mucosa Respiratoria/inmunología , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Interacciones Huésped-Patógeno , Humanos , Inmunidad Innata , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Especies Reactivas de Oxígeno/metabolismo , Receptores de Interleucina-8A/inmunología , Mucosa Respiratoria/microbiología , Receptor Toll-Like 5/genética , Receptor Toll-Like 5/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Large nonhealing ulcers and wounds frequently pose a great therapeutic challenge to clinicians and often require skin grafting. Various skin grafting methods are available to cover large skin defects that fail to epithelize. These methods include the use of small pinch grafts, full-thickness punch grafts, large-sized full-thickness grafts and split-thickness grafts. Large-sized full-thickness and split-thickness skin grafting requires expertise to produce cosmetically acceptable results and prevent cobblestoning, unlike small pinch and full-thickness punch grafts. OBJECTIVES: To describe a modified technique of split-thickness skin grafting that can be considerably faster than alternative methods. METHODS: We describe a method for split-thickness skin grafting using tumescent anaesthesia at the donor site and an electrodermatome and a polyurethane membrane without sutures at the site of the skin defect. RESULTS: Since 1997, we have practised a modified, improved, quick and easy split-thickness skin grafting method to cover large skin defects at the extremities. Complete healing is usually achieved 4-6 weeks after the split-thickness skin transplantation, and long-term results are aesthetically successful. CONCLUSIONS: We provide a sophisticated modified split-thickness skin graft procedure that has been practised for many years and provides cosmetically acceptable results while saving time.
Asunto(s)
Trasplante de Piel/métodos , Colgajos Quirúrgicos , Cicatrización de Heridas/fisiología , Anestesia Local/métodos , Humanos , Infusiones Subcutáneas , Poliuretanos/uso terapéutico , Técnicas de Cierre de HeridasAsunto(s)
Anticoagulantes/efectos adversos , Dalteparina/efectos adversos , Heparina de Bajo-Peso-Molecular/efectos adversos , Urticaria/inducido químicamente , Adulto , Antígenos CD/análisis , Biopsia , Femenino , Humanos , Pruebas Cutáneas/efectos adversos , Urticaria/inmunología , Urticaria/patologíaRESUMEN
Polymorphonuclear leukocytes (PMNs) characterize the pathology of T cell-mediated autoimmune diseases and delayed-type hypersensitivity reactions (DTHRs) in the skin, joints, and gut, but are absent in T cell-mediated autoimmune diseases of the brain or pancreas. All of these reactions are mediated by interferon gamma-producing type 1 T cells and produce a similar pattern of cytokines. Thus, the cells and mediators responsible for the PMN recruitment into skin, joints, or gut during DTHRs remain unknown. Analyzing hapten-induced DTHRs of the skin, we found that mast cells determine the T cell-dependent PMN recruitment through two mediators, tumor necrosis factor (TNF) and the CXC chemokine macrophage inflammatory protein 2 (MIP-2), the functional analogue of human interleukin 8. Extractable MIP-2 protein was abundant during DTHRs in and around mast cells of wild-type (WT) mice but absent in mast cell-deficient WBB6F(1)-Kit(W)/Kit(W-)(v) (Kit(W)/Kit(W)(-v)) mice. T cell-dependent PMN recruitment was reduced >60% by anti-MIP-2 antibodies and >80% in mast cell-deficient Kit(W)/Kit(W)(-v) mice. Mast cells from WT mice efficiently restored DTHRs and MIP-2-dependent PMN recruitment in Kit(W)/Kit(W)-(v) mice, whereas mast cells from TNF(-/)- mice did not. Thus, mast cell-derived TNF and MIP-2 ultimately determine the pattern of infiltrating cells during T cell-mediated DTHRs.