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Updated: Aug 30, 2026
Experimental Analysis of Apoptotic Thymocyte Engulfment by Macrophages
Published on: May 24, 2019
Resident murine alveolar and peritoneal macrophages differ in adhesion of apoptotic thymocytes
Bin Hu1, Jeffrey H Jennings, Joanne Sonstein
1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI 48105-2303, USA.
Abstract:
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.
Insights
Macrophages (Mø) clear apoptotic cells to prevent autoimmunity. Lung macrophages (AMø) are deficient in clearing these cells compared to peritoneal macrophages (PMø), with distinct adhesion mechanisms.
Area of Science:
- Immunology
- Cell Biology
- Respiratory Medicine
Background:
- Efficient clearance of apoptotic cells by macrophages (Mø) is crucial for preventing autoimmunity.
- However, apoptotic cell ingestion impairs macrophage microbicidal function.
- Murine alveolar macrophages (AMø) exhibit a specific deficiency in apoptotic cell ingestion compared to peritoneal macrophages (PMø).
Purpose of the Study:
- To further characterize the deficiency in apoptotic cell ingestion by murine alveolar macrophages (AMø).
- To compare the adhesion mechanisms of apoptotic cells by AMø and resident peritoneal macrophages (PMø).
Main Methods:
- In vitro static adhesion assays using apoptotic thymocytes and resident AMø and PMø from C57BL/6 mice.
- Assessment of the role of MerTK, surfactant protein A, cations, integrins, scavenger receptors, and CD11c/CD18 in apoptotic cell adhesion.
- Analysis of phagocytosis inhibition by specific antibodies.
Main Results:
- Apoptotic cell adhesion was rapid, specific, and cold-sensitive for both AMø and PMø.
- MerTK antibody blocked phagocytosis but not adhesion; surfactant protein A enhanced AMø adhesion and phagocytosis, but not to PMø levels.
- Adhesion mechanisms differed: cation-independent for PMø, calcium-dependent for AMø; AMø adhesion involved CD11c/CD18, unlike PMø.
Conclusions:
- Murine tissue macrophages utilize distinct receptor systems for apoptotic cell binding.
- The reduced capacity of AMø to ingest apoptotic cells is only partially explained by diminished initial adhesion.
- Understanding these differential mechanisms is key to addressing impaired efferocytosis in lung immunity.
