title: IL-10 protects monocytes and macrophages from complement-mediated lysis.
abstract: Phagocytes, such as monocytes and macrophages, are important cells of the innate immunity in the defense against microbes. So far, it is unclear how these cells survive at the site of combat against microbes, where a hostile inflammatory environment prevails with strong complement activity. We hypothesized that IL-10, a key cytokine involved in the resolution of inflammation, induces resistance to complement attack. Here, we demonstrate for the first time such a cell-protective effect of IL-10 on human monocytes and macrophages. IL-10 is indeed able to protect these cell types in an in vitro model of complement lysis triggered by an anti-MHCI antibody or by binding of zymosan. Investigating potential underlying mechanisms, we found that IL-10 up-regulated the expression of complement regulatory membrane protein CD59 and the general cell-protective stress protein HO-1 in human monocytes. However, further functional analysis failed to link these individual IL-10-mediated effects with the increased protection from complement lysis. Blocking the protective effect of CD59 with an antibody increased complement lysis but did not abrogate the IL-10-protective effect. Interestingly, chemical interference with HO-1 activity did abrogate the protective effect of IL-10, but siRNA-mediated knockdown of HO-1 did not confirm this observation. Our results suggest that IL-10 generates pathogen-clearing phagocytes, which are resistant to complement lysis and thereby, enabled to survive longer in a hostile inflammatory environment.
authors.affiliation: Institute of Medical Immunology, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Koch
authors.forename: Mechthild
authors.initials: M
authors.lastname: Jung
authors.forename: Robert
authors.initials: R
authors.lastname: Sabat
authors.forename: Jörn
authors.initials: J
authors.lastname: Krätzschmar
authors.forename: Wolf-Dietrich
authors.initials: WD
authors.lastname: Döcke
authors.forename: Khusru
authors.initials: K
authors.lastname: Asadullah
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Gerald
authors.initials: G
authors.lastname: Grütz
mesh_terms: D018957:CD59 Antigens / Q000096:biosynthesis; D016923:Cell Death; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000502:physiology*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology; D016753:Interleukin-10 / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D010586:Phagocytes; D020011:Protective Agents / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018957:CD59 Antigens; D020011:Protective Agents; D016753:Interleukin-10; D003165:Complement System Proteins; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1