ABSTRACT
T cells have a critical role in immune surveillance at mucosal surfaces. SHIP1(-/-) mice succumb to mucosal inflammatory disease that afflicts the lung and small intestine (SI). The basis of this condition has not been defined. Here we show that SHIP1 is required for the normal persistence and survival of T cells in mucosal tissues. We find that CD4 and CD8 effector T cells are reduced; however, Treg cells are increased in the SI and lungs of SHIP1(-/-) and CD4CreSHIP(flox/flox) mice. Furthermore, a subset of T cells in the SI of SHIP1(-/-) mice are FasL(+) and are more susceptible to extrinsic cell death. Mechanistic analyses showed that SHIP1 associates with the death receptor CD95/Fas and treatment with a Caspase 8 inhibitor prevents SHIP1 inhibitor-mediated T-cell death. Notably, mucosal inflammation in SHIP1(-/-) mice is reduced by treatment with a Caspase 8 inhibitor. We also find that the incidence of Crohn's disease (CD) and pneumonia is significantly increased in mice with dual T and myeloid lineage SHIP1 deletion but not in single lineage-deleted mice. Thus, by promoting survival of protective T cells, thereby preventing an inflammatory myeloid response, SHIP1 maintains an appropriate balance of innate immune function at mucosal surfaces necessary for immune homeostasis.
Subject(s)
Crohn Disease/immunology , Intestinal Mucosa/immunology , Phosphoric Monoester Hydrolases/immunology , Pneumonia/immunology , Respiratory Mucosa/immunology , T-Lymphocytes/immunology , Animals , Caspase 8/genetics , Caspase 8/immunology , Cell Survival/genetics , Cell Survival/immunology , Crohn Disease/genetics , Crohn Disease/pathology , Fas Ligand Protein/genetics , Fas Ligand Protein/immunology , Inositol Polyphosphate 5-Phosphatases , Intestinal Mucosa/pathology , Mice , Mice, Knockout , Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases , Phosphoric Monoester Hydrolases/genetics , Pneumonia/genetics , Respiratory Mucosa/pathology , T-Lymphocytes/pathology , fas Receptor/genetics , fas Receptor/immunologyABSTRACT
The second-generation air-Q intubating laryngeal airway is a newer commercially available supraglottic airway device. In this retrospective review, we describe our initial clinical experience of 70 insertions. The ease and number of insertion attempts, airway leak pressure, device positioning, duration of use, success of fibreoptic-aided intubation and oropharyngeal morbidity were recorded. The intubating laryngeal airway was successfully inserted in all 770 patients and functioned adequately as a primary airway in all 57 patients in which it was used. The median airway leak pressure was 25 and 30 cmH2O for the single-use and reusable devices (P = 0.001), respectively. Fibreoptic-aided intubation using the intubating laryngeal airway as a conduit was successful in 12/13 (92%) cases. One in four (26%) patients complained of mild sore throat postoperatively before discharge. In our series, the intubating laryngeal airway performed adequately as a primary airway during anaesthesia with respect to ease of insertion, adequacy of airway maintenance, and as a conduit for intubation in both anticipated and unanticipated difficult airways. Further investigation is warranted regarding the role of the intubating laryngeal airway as a conduit for both blind and fibreoptic-aided intubation. In addition, the incidence of postoperative throat complaints deserves further scrutiny.
