title: Maxed out macs: physiologic cell clearance as a function of macrophage phagocytic capacity.
abstract: The phagocytic clearance of host cells is important for eliminating dying cells and for the therapeutic clearance of antibody-targeted cells. As ubiquitous, motile and highly phagocytic immune cells, macrophages are principal players in the phagocytic removal of host cells throughout the body. In recent years, great strides have been made in identifying the molecular mechanisms that control the recognition and phagocytosis of cells by macrophages. However, much less is known about the physical and metabolic constraints that govern the amount of cellular material macrophages can ingest and how these limitations affect the overall efficiency of host cell clearance in health and disease. In this review we will discuss, in the contexts of apoptotic cells and antibody-targeted malignant cells, how physical and metabolic factors associated with the internalization of host cells are relayed to the phagocytic machinery and how these signals can impact the overall efficiency of cell clearance. We also discuss how this information can be leveraged to increase cell clearance for beneficial therapeutic outcomes.
authors.affiliation: Wilmot Cancer Institute, University of Rochester Medical Center, NY, USA.
authors.forename: Clive S
authors.initials: CS
authors.lastname: Zent
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, NY, USA.|David H. Smith Center for Vaccine Biology and Immunology, University of Rochester School of Medicine and Dentistry, NY, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Elliott
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018920:Coculture Techniques; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects*; D010743:Phospholipids / Q000378:metabolism; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D020690:GTPase-Activating Proteins; D010743:Phospholipids; C107953:RAC1 protein, human; D011961:Receptors, Fc; C480633:SLC2A4RG protein, human; D014157:Transcription Factors; D020830:rac1 GTP-Binding Protein
keywords: GTPase; apoptosis; cellular metabolism; chronic lymphocytic leukemia; efferocytosis; lymphoid malignancy; macrophage; monoclonal antibody therapy; phagocytosis