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Published ahead of print on October 3, 2003, doi:10.1165/rcmb.2003-0255OC

Am. J. Respir. Cell Mol. Biol., Volume 30, Number 5, May 2004, 687-693

A more recent version of this article appeared on May 1, 2004
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Submitted on July 7, 2003
Revised on October 1, 2003

Resident murine alveolar and peritoneal macrophages differ in adhesion of apoptotic thymocytes

Bin Hu1, Jeffrey H Jennings1, Joanne Sonstein1, Joanna Floros2, Jill C Todt1, Timothy Polak3, and Jeffrey L Curtis3*

1 Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA, 2 Cellular and Molecular Physiology, Penn State College of Medicine, Hershey, PA, USA; Pediatrics, Penn State College of Medicine, Hershey, PA, USA; Obstetrics and Gynecology, Penn State College of Medicine, Hershey, PA, USA, 3 Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA; Medical Service, Department of Veterans Affairs, Ann Arbor, MI, USA

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

Apoptotic cells must be cleared efficiently by macrophages (M{phi}) to prevent autoimmunity, yet their ingestion impairs M{phi} microbicidal function. The principal murine resident lung phagocyte, the alveolar M{phi} (AM{phi}), is specifically deficient at apoptotic cell ingestion, both in vitro and in vivo, compared to resident peritoneal M{phi} (PM{phi}). To further characterize this deficiency, we assayed static adhesion in vitro using apoptotic thymocytes and resident AM{phi} and PM{phi} from normal C57BL/6 mice. Adhesion of apoptotic thymocytes by both types of M{phi} was rapid, specific, and cold-sensitive. Antibody against the receptor tyrosine kinase MerTK (Tyro12) blocked phagocytosis but not adhesion in both types of M{phi}. Surfactant protein A increased adhesion and phagocytosis by AM{phi}, but not to the levels seen using PM{phi}. Adhesion was largely cation-independent for PM{phi} and calcium-dependent for AM{phi}. Adhesion was not inhibited in either M{phi} type by mAbs against {beta}1 or {beta}3 integrins or scavenger receptor I/II (CD204), but AM{phi} adhesion was inhibited by specific mAbs against CD11c/CD18. Thus, resident murine tissue M{phi} from different tissues depend on qualitatively disparate receptors systems to bind apoptotic cells. The decreased capacity of murine AM{phi} to ingest apoptotic cells is only partially explained by reduced initial adhesion.




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