Anner following production from other cell forms. Bone marrow, endothelial cells, and vascular smooth muscle cells expressVOLUME 8 Number 5 SEPTEMBER 2015 www.nature.com/miARTICLESFigure 7 Elevated severity of viral lung disease in influenza-infected Axl / mice regardless of effective clearance of viruses. (a) Alter in body mass of HSP90 Activator supplier wild-type (WT; closed symbol) and Axl / (open symbol) mice infected with 7.5 p.f.u. influenza. Level of interleukin (IL)-6 (b) and chemokine (C-C motif) ligand 2 (CCL-2) (c) inside the bronchoairway lavage (BAL) fluid recovered on day 12 post influenza infection from WT and Axl / mice. (d) Analysis of viable cells within the BAL from WT and Axl / mice recovered on day 12 post influenza infection and counted using trypan blue exclusion. (e) Flow cytometric analysis of numbers of (e) neutrophils, (f) CD4 T cells, and (g) CD8 T cells within the BAL from WT and Axl / mice on day 12 post influenza infection. (h) Influenza genomic mRNA copies recovered in the total lung of WT and Axl / mice on days four and 8 post influenza infection. (i and j) Flow cytometric analysis of percentage of (i) early (Annexin V propidium iodide (PI)) and (j) late (Annexin V PI) apoptotic lymphocytes in the in the BAL from WT and Axl / mice on day 10 post influenza infection. (k) Volume of nucleosomes released in the BAL fluid recovered from WT and Axl / mice on day 0 (naive) and day 12 post influenza infection. (l) Efficiency of uptake of apoptotic thymocytes by WT (filled bar) and Axl / (open bar) airway macrophages measured by flow cytometry. (a and k) are representative of two or three independent experiments with 92 mice per group. (i,j) Data from one particular experiment with ten mice per group. (h,l) Representative of two independent experiments with four or five mice per group. Po0.05, Po0.01, Po0.001, Po0.0001 vs. corresponding group; unpaired t-test.Gas6 (refs 235) and we are the initial to show differential expression of Gas6 in certain macrophage subsets, i.e., CD11bhiCD11cintermediate monocyte/macrophages, but not CD11bloCD11chi airway macrophages. This is most likely to lead to functional polarization of macrophages depending on their anatomical location. Though all airway macrophages also express a second TAM receptor, MerTK, Gas6 binding was lost in Axl / macrophages, supporting the idea that Axl is the highest affinity ETB Agonist Storage & Stability receptor for this PtdSer-binding ligand,26 and suggesting a distinctive and non-redundant function of Axl and MerTK in regulating responses to apoptotic cells. In a recently proposed model, Axl includes a dominant part in apoptotic cell uptake by macrophages below inflammatory circumstances, whereas MerTK mediates macrophage responses to apoptoticMucosalImmunology VOLUME eight Number five SEPTEMBERcells in homeostasis and throughout immunosuppression.five Consistently, we observed induction of Axl expression on macrophages by inflammatory stimuli in vitro and upon viral infection in vivo. We’ve also found that GM-CSF induces Axl expression on peritoneal macrophages and BMDMs. GM-CSF is produced by a variety of cells, considerably airway epithelial kind II cells,27 and is essential for airway macrophage development18 as well as the protection of airway epithelial integrity.19 GM-CSF / mice lack airway macrophages19 along with the presence of GM-CSF autoantibodies or mutations inside the GM-CSF receptor a or b chain results in pulmonary airway proteinosis,28 a situation characterized by insufficient surfactant clearance by airway macrophages. Furthermore, GM-CSF-deficient miceARTICLE.
