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Published ahead of print on November 24, 2004, doi:10.1165/rcmb.2004-0108OC

Am. J. Respir. Cell Mol. Biol., Volume 32, Number 2, February 2005, 108-117

A more recent version of this article appeared on February 1, 2005
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Submitted on April 2, 2004
Revised on November 24, 2004

Monocytes recruited to the lungs of mice during immune inflammation ingest apoptotic cells poorly

Jeffrey H Jennings1, Derek J Linderman2, Bin Hu1, Joanne Sonstein1, and Jeffrey L Curtis3*

1 Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA, 2 The Pulmonary and Critical Care Medicine Section, Medical Service, Department of Veterans Affairs, Ann Arbor, MI, USA, 3 Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA; The Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, MI, USA; The Graduate Program in Immunology, University of Michigan Health System, Ann Arbor, MI, USA

* To whom correspondence should be addressed. E-mail: jlcurtis{at}umich.edu.

Apoptotic cells must be cleared to resolve inflammation, but few resident alveolar macrophages (AM{phi}) from normal lungs ingest apoptotic cells. We examined how M{phi} ingestion of apoptotic cells is altered during immune inflammation induced by intratracheal (IT) challenge of primed C57BL/6 mice using sheep red blood cells. Resident AM{phi} were labeled 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. ITchallenge induced rapid recruitment of monocytes, peaking at day 3 and decreasing thereafter, whereas numbers of resident AM{phi} did not change significantly. At all times, the percentage of phagocytes ingesting apoptotic thymocytes in vitro was greater among resident AM{phi} (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 non-significant trend towards lower ingestion by monocytes in vivo. MerTK, a receptor tyrosine kinase crucial for apoptotic cell phagocytosis, was expressed by resident AM{phi}, but not by recruited monocytes. Relative to resident AM{phi}, monocytes recruited to the alveolus ingest apoptotic cells meagerly, possibly due to absence of MerTK expression.




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