Many of the biological properties of C5a are mediated through activation of its receptor (C5aR1), the expression of which has been demonstrated convincingly on myeloid cells, such as neutrophils, monocytes, and macrophages. In contrast, conflicting results exist regarding C5aR1 expression in dendritic cells (DCs) and lymphoid lineage cells. In this article, we report the generation of a floxed GFP-C5aR1 reporter knock-in mouse. Using this mouse strain, we confirmed strong C5aR1 expression in neutrophils from bone marrow, blood, lung, and spleen, as well as in peritoneal macrophages. Further, we show C5aR1 expression in lung eosinophils, lung- and lamina propria–resident and alveolar macrophages, bone marrow–derived DCs, and lung-resident CD11b+ and monocyte-derived DCs, whereas intestinal and pulmonary CD103+ DCs stained negative. Also, some splenic NKT cells expressed GFP, whereas naive NK cells and B2 cells lacked GFP expression. Finally, we did not observe any C5aR1 expression in naive or activated CD4+ Th cells in vitro or in vivo. Mating the floxed GFP-C5aR1 mouse strain with LysMCre mice, we were able to specifically delete C5aR1 in neutrophils and macrophages, whereas C5aR1 expression was retained in DCs. In summary, our findings suggest that C5aR1 expression in mice is largely restricted to cells of the myeloid lineage. The novel floxed C5aR1 reporter knock-in mouse will prove useful to track C5aR1 expression in experimental models of acute and chronic inflammation and to conditionally delete C5aR1 in immune cells.

Introduction Acute respiratory distress syndrome (ARDS) is a complex clinical syndrome characterized by acute inflammation, microvascular damage, and increased pulmonary vascular and epithelial permeability, frequently resulting in acute respiratory failure and death. Current best practice for ARDS involves “lung-protective ventilation,” which entails low tidal volumes and limiting the plateau pressures in mechanically ventilated patients. Although considerable progress has been made in understanding the pathogenesis of ARDS, little progress has been made in the development of specific therapies to combat injury and inflammation. Areas Covered In recent years, several natural products have been studied in experimental models and have been shown to inhibit multiple inflammatory pathways associated with acute lung injury and ARDS at a molecular level. Because of the pleiotropic effects of these agents, many of them also activate antioxidant pathways through nuclear factor erythroid-related factor 2, thereby targeting multiple pathways. Several of these agents are prescribed for treatment of inflammatory conditions in the Asian subcontinent and have shown to be relatively safe. Expert Commentary Here we review natural remedies shown to attenuate lung injury and inflammation in experimental models. Translational human studies in patients with ARDS may facilitate treatment of this devastating disease.

Extracorporeal membrane oxygenation can be used to safely bridge high-acuity patients with end-stage lung disease to lung transplantation with good 30-day, 90-day, and 1-year survival and excellent 1-year functional status. Long-term outcomes are being studied.

Pulmonary artery pseudoaneurysm (PAPA), an uncommon complication of pyogenic bacterial and fungal infections and related septic emboli, is associated with high mortality. The pulmonary artery (PA) lacks an adventitial wall; therefore, repeated endovascular seeding of the PA with septic emboli creates saccular dilations that are more likely to rupture than systemic arterial aneurysms. The most common clinical presentation of PAPA is massive hemoptysis and resultant worsening hypoxemia. Computed tomography angiography is the preferred diagnostic modality for PAPA; typical imaging patterns include focal outpouchings of contrast adjacent to a branch of the PA following the same contrast density as the PA in all phases of the study. In mycotic PAPAs, multiple synchronous lesions are often seen in segmental and subsegmental PAs due to ongoing embolic phenomena. The recommended approach for a mycotic PAPA is prolonged antimicrobial therapy; for massive hemoptysis, endovascular treatment (e.g., coil embolization, stenting, or embolization of the feeding vessel) is preferred. PAPA resection and lobectomy are a last resort, generally reserved for patients with uncontrolled hemoptysis or pleural hemorrhage. We present a case of a 28-year-old woman with necrotizing pneumonia from intravenous drug use who ultimately died from massive hemoptysis and shock after a ruptured PAPA.

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