Published ahead of print on October 3, 2003, doi:10.1165/rcmb.2003-0255OC
American Journal of Respiratory Cell and Molecular Biology. Vol. 30, pp. 687-693, 2004
© 2004 American Thoracic Society DOI: 10.1165/rcmb.2003-0255OC
Resident Murine Alveolar and Peritoneal Macrophages Differ in Adhesion of Apoptotic Thymocytes
Bin Hu,
Jeffrey H. Jennings,
Joanne Sonstein,
Joanna Floros,
Jill C. Todt,
Timothy Polak and
Jeffrey L. Curtis
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System; and Pulmonary and Critical Care Medicine Section, Medical Service, Department of Veterans Affairs Medical Center, Ann Arbor, Michigan; and Departments of Cellular and Molecular Physiology, Pediatrics, and Obstetrics and Gynecology, Penn State College of Medicine, Hershey, Pennsylvania
Address correspondence to: Jeffrey L. Curtis, M.D., Pulmonary and Critical Care Medicine Section (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 efficiently by macrophages (Mø) to prevent autoimmunity, yet their ingestion impairs Mø microbicidal function. The principal murine resident lung phagocyte, the alveolar Mø (AMø), is specifically deficient at apoptotic cell ingestion, both in vitro and in vivo, compared with resident peritoneal Mø (PMø). To further characterize this deficiency, we assayed static adhesion in vitro using apoptotic thymocytes and resident AMø and PMø from normal C57BL/6 mice. Adhesion of apoptotic thymocytes by both types of Mø was rapid, specific, and cold-sensitive. Antibody against the receptor tyrosine kinase MerTK (Tyro12) blocked phagocytosis but not adhesion in both types of Mø. Surfactant protein A increased adhesion and phagocytosis by AMø, but not to the levels seen using PMø. Adhesion was largely cation-independent for PMø and calcium-dependent for AMø. Adhesion was not inhibited in either Mø type by mAbs against ß1 or ß3 integrins or scavenger receptor I/II (CD204), but AMø adhesion was inhibited by specific mAbs against CD11c/CD18. Thus, resident murine tissue Mø from different tissues depend on qualitatively disparate receptor systems to bind apoptotic cells. The decreased capacity of murine AMø to ingest apoptotic cells is only partially explained by reduced initial adhesion.
Abbreviations: activation-induced cell death, AICD alveolar macrophage, AMø bronchoalveolar lavage, BAL fetal bovine serum, FBS human monocyte-derived macrophage, HMDM monoclonal antibody, mAb murine bone marrowderived macrophage, MBMDM peritoneal macrophage, PMø phosphatidylserine, PS PS receptor, PS-R
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