Monocytes recruited to the lungs of mice during immune inflammation ingest apoptotic cells poorly.
Apoptotic cells must be cleared to resolve inflammation, but few resident alveolar macrophages (AMo) from normal lungs ingest apoptotic cells. We examined how Mo ingestion of apoptotic cells is altered during immune inflammation induced by intratracheal challenge of primed C57BL/6 mice using sheep red blood cells. Resident AMo were labeled in situ before challenge using intravenous PKH26 to distinguish them from recruited monocytes. Using flow cytometry, we identified phagocytosis of fluorescently-labeled apoptotic thymocytes by alveolar mononuclear phagocytes in vitro and in vivo, and measured surface molecule expression. Intratracheal challenge induced rapid recruitment of monocytes, peaking at Day 3 and decreasing thereafter, whereas numbers of resident AMo did not change significantly. At all times, the percentage of phagocytes ingesting apoptotic thymocytes in vitro was greater among resident AMo (28-45%) than among recruited monocytes (9-19%), but was low in both cell types relative to ingestion of immunoglobulin-opsonized targets. There was also a nonsignificant trend toward lower ingestion by monocytes in vivo. MerTK, a receptor tyrosine kinase crucial for apoptotic cell phagocytosis, was expressed by resident AMo, but not by recruited monocytes. Relative to resident AMo, monocytes recruited to the alveolus ingest apoptotic cells meagerly, possibly due to absence of MerTK expression.
Jennings
Jeffrey H
JH
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI 48105, USA.
Linderman
Derek J
DJ
Hu
Bin
B
Sonstein
Joanne
J
Curtis
Jeffrey L
JL
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008262:Macrophage Activation / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000473:pathology; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology*; D011518:Proto-Oncogene Proteins / Q000276:immunology; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology; D012756:Sheep; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D000076202:c-Mer Tyrosine Kinase
D011518:Proto-Oncogene Proteins; C490767:Mertk protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase