Published ahead of print on November 24, 2004, doi:10.1165/rcmb.2004-0108OC
© 2005 American Thoracic Society DOI: 10.1165/rcmb.2004-0108OC Monocytes Recruited to the Lungs of Mice during Immune Inflammation Ingest Apoptotic Cells PoorlyDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine; the Comprehensive Cancer Center, and the Graduate Program in Immunology, University of Michigan Health System; and the Pulmonary and Critical Care Medicine Section, Medical Service, Department of Veterans Affairs Medical Center, Ann Arbor, Michigan Correspondence and requests for reprints should be addressed to Jeffrey L. Curtis, M.D., Pulmonary & Critical Care Medicine Section (506/111G), Department of Veterans Affairs Medical Center, 2215 Fuller Road; Ann Arbor, MI 48105-2303. E-mail: jlcurtis{at}umich.edu Apoptotic cells must be cleared to resolve inflammation, but few resident alveolar macrophages (AMø) from normal lungs ingest apoptotic cells. We examined how Mø ingestion of apoptotic cells is altered during immune inflammation induced by intratracheal challenge of primed C57BL/6 mice using sheep red blood cells. Resident AMø 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 AMø did not change significantly. At all times, the percentage of phagocytes ingesting apoptotic thymocytes in vitro was greater among resident AMø (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 AMø, but not by recruited monocytes. Relative to resident AMø, monocytes recruited to the alveolus ingest apoptotic cells meagerly, possibly due to absence of MerTK expression.
Key Words: apoptosis • adhesion molecules • mice, inbred strains • macrophage • receptor tyrosine kinase This article has been cited by other articles:
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