Resident murine alveolar and peritoneal macrophages differ in adhesion of apoptotic thymocytes.
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 beta1 or beta3 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.
Hu
Bin
B
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI 48105-2303, USA.
Jennings
Jeffrey H
JH
Sonstein
Joanne
J
Floros
Joanna
J
Todt
Jill C
JC
Polak
Timothy
T
Curtis
Jeffrey L
JL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D039521:CD11c Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D003080:Cold Temperature; D005260:Female; D016676:Macrophages, Alveolar / Q000166:cytology / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011518:Proto-Oncogene Proteins; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology*; D000076202:c-Mer Tyrosine Kinase
D000911:Antibodies, Monoclonal; D039521:CD11c Antigen; D018821:CD18 Antigens; D002412:Cations; D011518:Proto-Oncogene Proteins; D037662:Pulmonary Surfactant-Associated Protein A; C490767:Mertk protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase; D002118:Calcium