title: Liposomes of phosphatidylcholine and cholesterol induce an M2-like macrophage phenotype reprogrammable to M1 pattern with the involvement of B-1 cells.
abstract: Macrophages respond to endogenous and non-self stimuli acquiring the M1 or M2 phenotypes, corresponding to classical or alternative activation, respectively. The role of B-1 cells in the regulation of macrophage polarization through the secretion of interleukin (IL)-10 has been demonstrated. However, the influence of B-1 cells on macrophage phenotype induction by an immunogen that suppress their ability to secrete IL-10 has not been explored. Here, we studied the peritoneal macrophage pattern induced by liposomes comprised of dipalmitoylphosphatidylcholine (DPPC) and cholesterol (Chol) carrying ovalbumin (OVA) (Lp DPPC/OVA), and the involvement of B-1 cells in macrophage polarization. Peritoneal cells from BALB/c, B-1 cells-deficient BALB/xid and C57BL/6 mice immunized with Lp DPPC/OVA and OVA in soluble form (PBS/OVA) were analyzed and stimulated or not in vitro with lipopolysaccharide (LPS). Peritoneal macrophages from BALB/c and C57BL/6 mice immunized with Lp DPPC/OVA showed an M2-like phenotype as evidenced by their high arginase activity without LPS stimulation. Upon stimulation, these macrophages were reprogrammable toward the M1 phenotype with the upregulation of nitric oxide (NO) and a decrease in IL-10 secretion. In addition, high IFN-γ levels were detected in the culture supernatant of peritoneal cells from BALB/c and C57BL/6 mice immunized with Lp DPPC/OVA. Nevertheless, still high levels of arginase activity and undetectable levels of IL-12 were found, indicating that the switch to a classical activation state was not complete. In the peritoneal cells from liposomes-immunized BALB/xid mice, levels of arginase activity, NO, and IL-6 were below those from wild type animals, but the last two products were restored upon adoptive transfer of B-1 cells, together with an increase in IFN-γ secretion. Summarizing, we have demonstrated that Lp DPPC/OVA induce an M2-like pattern in peritoneal macrophages reprogrammable to M1 phenotype after LPS stimulation, with the involvement of B-1 cells.
authors.affiliation: Center for Protein Studies, Faculty of Biology, University of Havana, Havana 10400, Cuba.
authors.forename: Yoelys
authors.initials: Y
authors.lastname: Cruz-Leal
authors.affiliation: Immunology Discipline, Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP) Paulista Medicine School, São Paulo 04023-062, São Paulo, Brazil.
authors.forename: María Fernanda
authors.initials: MF
authors.lastname: Lucatelli Laurindo
authors.affiliation: Immunology Discipline, Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP) Paulista Medicine School, São Paulo 04023-062, São Paulo, Brazil.
authors.forename: Lika
authors.initials: L
authors.lastname: Osugui
authors.affiliation: Center for Protein Studies, Faculty of Biology, University of Havana, Havana 10400, Cuba.
authors.forename: María Del Carmen
authors.initials: Mdel C
authors.lastname: Luzardo
authors.affiliation: Research Division, Center of Molecular Immunology (CIM), Havana 11600, Cuba.
authors.forename: Alejandro
authors.initials: A
authors.lastname: López-Requena
authors.affiliation: Center for Protein Studies, Faculty of Biology, University of Havana, Havana 10400, Cuba.
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Alonso
authors.affiliation: Center for Protein Studies, Faculty of Biology, University of Havana, Havana 10400, Cuba.
authors.forename: Carlos
authors.initials: C
authors.lastname: Álvarez
authors.affiliation: Immunology Discipline, Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP) Paulista Medicine School, São Paulo 04023-062, São Paulo, Brazil.
authors.forename: Ana Flavia
authors.initials: AF
authors.lastname: Popi
authors.affiliation: Immunology Discipline, Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP) Paulista Medicine School, São Paulo 04023-062, São Paulo, Brazil.
authors.forename: Mario
authors.initials: M
authors.lastname: Mariano
authors.affiliation: Research Division, Center of Molecular Immunology (CIM), Havana 11600, Cuba. Electronic address: rolando@cim.sld.cu.
authors.forename: Rolando
authors.initials: R
authors.lastname: Pérez
authors.affiliation: Center for Protein Studies, Faculty of Biology, University of Havana, Havana 10400, Cuba. Electronic address: mlanio@fbio.uh.cu.
authors.forename: María Eliana
authors.initials: ME
authors.lastname: Lanio
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000494:pharmacology; D019264:Adoptive Transfer; D000818:Animals; D001119:Arginase / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000494:pharmacology*; D004337:Drug Carriers / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology; D008081:Liposomes / Q000494:pharmacology*; D008262:Macrophage Activation / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009569:Nitric Oxide / Q000096:biosynthesis; D010047:Ovalbumin / Q000494:pharmacology*; D010641:Phenotype; D010713:Phosphatidylcholines / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; C556062:IL10 protein, mouse; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008081:Liposomes; D010713:Phosphatidylcholines; D016753:Interleukin-10; D018664:Interleukin-12; D015060:1,2-Dipalmitoylphosphatidylcholine; D009569:Nitric Oxide; D007371:Interferon-gamma; D010047:Ovalbumin; D002784:Cholesterol; D001119:Arginase
keywords: B-1 cells; Liposomes; Macrophage polarization