title: Serum-dependent processing of late apoptotic cells for enhanced efferocytosis.
abstract: Binding of the serum protein complement component C1q to the surface of dying cells facilitates their clearance by phagocytes in a process termed efferocytosis. Here, we investigate during which phase of apoptotic cell death progression C1q binding takes place. Purified C1q was found to bind to all dying cells and, albeit weaker, also to viable cells. The presence of serum abrogated completely the binding to viable cells. In addition, C1q binding to dying cells was limited to a specific subpopulation of late apoptotic/secondary necrotic cells. Co-culturing serum-treated apoptotic cells with human monocytes revealed a much higher phagocytosis of C1q-positive than of C1q-negative late apoptotic/secondary necrotic cells. But this phagocytosis-promoting activity could not be observed with purified C1q. Serum-treated C1q-positive late apoptotic/secondary necrotic cells exhibited a similar volume, a similar degraded protein composition, but a much lower DNA content in comparison with the remaining late apoptotic/secondary necrotic cells. This was mediated by a serum-bound nuclease activity that could be abrogated by G-actin, which is a specific inhibitor of serum DNase I. These results show that serum factors are involved in the prevention of C1q binding to viable cells and in the processing of late apoptotic/secondary necrotic cells promoting cell death progression toward apoptotic bodies. This process leads to the exposure of C1q-binding structures and facilitates efferocytosis.
authors.affiliation: Department of Surgery, Surgical Research Laboratories, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Liang
authors.affiliation: Department of Surgery, Surgical Research Laboratories, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Arnold
authors.affiliation: Department of Surgery, Surgical Research Laboratories, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Michlmayr
authors.affiliation: Department of Surgery, Surgical Research Laboratories, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: D
authors.initials: D
authors.lastname: Rainprecht
authors.affiliation: Department of Surgery, Surgical Research Laboratories, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Perticevic
authors.affiliation: Department of Surgery, Surgical Research Laboratories, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Spittler
authors.affiliation: Department of Surgery, Surgical Research Laboratories, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Oehler
mesh_terms: D017209:Apoptosis; D018920:Coculture Techniques; D015922:Complement C1q / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis
chemical_list: D015922:Complement C1q