Alveolar macrophages regulate neutrophil recruitment in endotoxin-induced lung injury

BACKGROUND: Alveolar macrophages play an important role during the development of acute inflammatory lung injury. In the present study, in vivo alveolar macrophage depletion was performed by intratracheal application of dichloromethylene diphosphonate-liposomes in order to study the role of these effector cells in the early endotoxin-induced lung injury. METHODS: Lipopolysaccharide was applied intratracheally and the inflammatory reaction was assessed 4 hours later. Neutrophil accumulation and expression of inflammatory mediators were determined. To further analyze in vivo observations, in vitro experiments with alveolar epithelial cells and alveolar macrophages were performed. RESULTS: A 320% increase of polymorphonuclear leukocytes in bronchoalveolar lavage fluid was observed in macrophage-depleted compared to macrophage-competent lipopolysaccharide-animals. This neutrophil recruitment was also confirmed in the interstitial space. Monocyte chemoattractant protein-1 concentration in bronchoalveolar lavage fluid was significantly increased in the absence of alveolar macrophages. This phenomenon was underlined by in vitro experiments with alveolar epithelial cells and alveolar macrophages. Neutralizing monocyte chemoattractant protein-1 in the airways diminished neutrophil accumulation. CONCLUSION: These data suggest that alveolar macorphages play an important role in early endotoxin-induced lung injury. They prevent neutrophil influx by controlling monocyte chemoattractant protein-1 production through alveolar epithelial cells. Alveolar macrophages might therefore possess robust anti-inflammatory effects

Changes in Inflammatory Response after Endovascular Treatment for Type B Aortic Dissection

This present study aims to investigate the changes in the inflammatory markers after elective endovascular treatment of Type B aortic dissection with aneurysm, as related to different anatomical features of the dissection flap in the paravisceral perfusion. Consecutive patients with type B aortic dissections with elective endovascular stent graft repair were recruited and categorized into different groups. Serial plasma levels of cytokines (Interleukin-1β, -6, -8, -10, TNF-α), chemokines (MCP-1), and serum creatinine were monitored at pre-, peri- and post-operative stages. The length of stent graft employed in each surgery was retrieved and correlated with the change of all studied biochemical parameters. A control group of aortic dissected patients with conventional medication management was recruited for comparing the baseline biochemical parameters. In total, 22 endovascular treated and 16 aortic dissected patients with surveillance were recruited. The endovascular treated patients had comparable baseline levels as the non-surgical patients. There was no immediate or thirty day-mortality, and none of the surgical patients developed post-operative mesenteric ischaemia or clinically significant renal impairment. All surgical patients had detectable pro-inflammatory mediators, but none of the them showed any statistical significant surge in the peri-operative period except IL-1β and IL-6. Similar results were obtained when categorized into different groups. IL-1β and IL-6 showed maximal levels within hours of the endovascular procedure (range, 3.93 to 27.3 higher than baseline; p = 0.001), but returned to baseline 1 day post-operatively. The change of IL-1β and IL-6 at the stent graft deployment was statistically greater in longer stent graft (p>0.05). No significant changes were observed in the serum creatinine levels. In conclusion, elective endovascular repair of type B aortic dissection associated with insignificant changes in inflammatory mediators and creatinine. All levels fell toward basal levels post-operatively suggesting that thoracic endovascular aortic repair is rather less aggressive with insignificant inflammatory modulation

Role of CFTR expressed by neutrophils in modulating acute lung inflammation and injury in mice

Objective and designCystic fibrosis transmembrane conductance regulator (CFTR) regulates infection and inflammation. In this study, we investigated whether a lack of functional CFTR in neutrophils would promote lipopolysaccharide (LPS)-induced lung inflammation and injury.Materials and methodsCFTR-inhibited or F508del-CFTR-mutated neutrophils were stimulated with LPS and cultured to evaluate production of cytokines and NF-κB activation. Wild-type mice were reconstituted with F508del neutrophils or bone marrow and then intratracheally challenged with LPS to observe lung inflammatory response.ResultsPharmacologic inhibition and genetic mutation of CFTR in neutrophils activated NF-κB and facilitated macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-α (TNF-α) production. Wild-type mice reconstituted with F508del neutrophils and bone marrow had more severe lung inflammation and injury after LPS challenge compared to wild-type mice receiving wild-type neutrophils or bone marrow reconstitution.ConclusionsLack of functional CFTR in neutrophils can promote LPS-induced acute lung inflammation and injury

Amyloid Precursor Protein Is Required for Normal Function of the Rod and Cone Pathways in the Mouse Retina

Amyloid precursor protein (APP) is a transmembrane glycoprotein frequently studied for its role in Alzheimer's disease. Our recent study in APP knockout (KO) mice identified an important role for APP in modulating normal neuronal development in the retina. However the role APP plays in the adult retina and whether it is required for vision is unknown. In this study we evaluated the role of APP in retinal function and morphology comparing adult wildtype (WT) and APP-KO mice. APP was expressed on neuronal cells of the inner retina, including horizontal, cone bipolar, amacrine and ganglion cells in WT mice. The function of the retina was assessed using the electroretinogram and although the rod photoreceptor responses were similar in APP-KO and WT mice, the post-photoreceptor, inner retinal responses of both the rod and cone pathways were reduced in APP-KO mice. These changes in inner retinal function did not translate to a substantial change in visual acuity as assessed using the optokinetic response or to changes in the gross cellular structure of the retina. These findings indicate that APP is not required for basic visual function, but that it is involved in modulating inner retinal circuitry