Anner immediately after production from other cell types. Bone marrow, endothelial cells, and vascular smooth muscle cells expressVOLUME 8 Quantity five SEPTEMBER 2015 www.nature.com/miARTICLESFigure 7 Improved severity of viral lung disease in influenza-infected Axl / mice in spite of efficient clearance of viruses. (a) Adjust in physique mass of wild-type (WT; closed symbol) and Axl / (open symbol) mice infected with 7.five p.f.u. influenza. Volume of interleukin (IL)-6 (b) and chemokine (C-C motif) ligand two (CCL-2) (c) within the bronchoBRPF3 Inhibitor drug airway lavage (BAL) fluid recovered on day 12 post influenza infection from WT and Axl / mice. (d) Analysis of viable cells inside the BAL from WT and Axl / mice recovered on day 12 post influenza infection and counted applying trypan blue exclusion. (e) Flow cytometric evaluation of numbers of (e) neutrophils, (f) CD4 T cells, and (g) CD8 T cells in the BAL from WT and Axl / mice on day 12 post influenza infection. (h) Influenza genomic mRNA copies recovered from the total lung of WT and Axl / mice on days four and eight 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) D4 Receptor Agonist Biological Activity apoptotic lymphocytes within the within the BAL from WT and Axl / mice on day ten post influenza infection. (k) Level 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 a single experiment with ten mice per group. (h,l) Representative of two independent experiments with 4 or five mice per group. Po0.05, Po0.01, Po0.001, Po0.0001 vs. corresponding group; unpaired t-test.Gas6 (refs 235) and we’re the initial to show differential expression of Gas6 in particular macrophage subsets, i.e., CD11bhiCD11cintermediate monocyte/macrophages, but not CD11bloCD11chi airway macrophages. This can be most likely to result in functional polarization of macrophages according to their anatomical location. Although all airway macrophages also express a second TAM receptor, MerTK, Gas6 binding was lost in Axl / macrophages, supporting the idea that Axl will be the highest affinity receptor for this PtdSer-binding ligand,26 and suggesting a one of a kind and non-redundant part of Axl and MerTK in regulating responses to apoptotic cells. Within a lately proposed model, Axl includes a dominant part in apoptotic cell uptake by macrophages under inflammatory conditions, whereas MerTK mediates macrophage responses to apoptoticMucosalImmunology VOLUME 8 Number five SEPTEMBERcells in homeostasis and through immunosuppression.five Consistently, we observed induction of Axl expression on macrophages by inflammatory stimuli in vitro and upon viral infection in vivo. We have also found that GM-CSF induces Axl expression on peritoneal macrophages and BMDMs. GM-CSF is created by a variety of cells, significantly airway epithelial kind II cells,27 and is vital for airway macrophage development18 plus the protection of airway epithelial integrity.19 GM-CSF / mice lack airway macrophages19 and also the presence of GM-CSF autoantibodies or mutations inside the GM-CSF receptor a or b chain results in pulmonary airway proteinosis,28 a condition characterized by insufficient surfactant clearance by airway macrophages. In addition, GM-CSF-deficient miceARTICLE.
