PMID- 31921135 OWN - NLM STAT- MEDLINE DCOM- 20201104 LR - 20201104 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 10 DP - 2019 TI - Heme-Oxygenase-1 Is Decreased in Circulating Monocytes and Is Associated With Impaired Phagocytosis and ROS Production in Lupus Nephritis. PG - 2868 LID - 10.3389/fimmu.2019.02868 [doi] LID - 2868 AB - Lupus nephritis (LN) is one of the most serious manifestations of systemic lupus erythematosus (SLE). Based on studies showing the potential role of heme oxygenase-1 (HO-1), an enzyme that catalyzes the degradation of heme and has anti-inflammatory properties in SLE development, we decided to explore HO-1 in LN. Accordingly, we evaluated HO-1 levels and function in circulating and infiltrating monocytes and neutrophils of LN patients. HO-1 levels were assessed in peripheral monocytes of LN patients and controls by flow cytometry and immunofluorescence microscopy. Phagocytosis and the production of reactive oxygen species (ROS) were evaluated to determine the effect of HO-1 in monocyte function. In addition, renal biopsies with proliferative LN were used to identify HO-1 in infiltrating cells and renal tissue by immunofluorescence and immunohistochemistry. Biopsies of healthy controls (HC) and patients who underwent nephrectomy were included as controls. Circulating pro-inflammatory monocytes and activated neutrophils were increased in LN patients. HO-1 levels were decreased in all subsets of monocytes and in activated neutrophils. LN monocytes showed increased phagocytosis and higher production of ROS than those of HC. When HO-1 was induced, phagocytosis and ROS levels became similar to those of HC. HO-1 was mostly expressed in renal tubular epithelial cells (RTEC). Renal tissue of LN patients showed lower levels of HO-1 than HC, whereas infiltrating immune cells of LN showed lower levels of HO-1 than biopsies of patients who had renal surgery. HO-1 is decreased in circulating monocytes and activated neutrophils of LN patients. HO-1 levels modulate the phagocytosis of LN monocytes and ROS production. HO-1 expression in RTEC might be an attempt of self-protection from inflammation. CI - Copyright (c) 2019 Cuitino, Obreque, Gajardo-Meneses, Villarroel, Crisostomo, San Francisco, Valenzuela, Mendez and Llanos. FAU - Cuitino, Loreto AU - Cuitino L AD - Departamento de Inmunologia Clinica y Reumatologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile. FAU - Obreque, Javiera AU - Obreque J AD - Departamento de Inmunologia Clinica y Reumatologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile. FAU - Gajardo-Meneses, Patricia AU - Gajardo-Meneses P AD - Departamento de Inmunologia Clinica y Reumatologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile. FAU - Villarroel, Alejandra AU - Villarroel A AD - Departamento de Anatomia Patologica, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile. FAU - Crisostomo, Natalia AU - Crisostomo N AD - Departamento de Inmunologia Clinica y Reumatologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile. FAU - San Francisco, Ignacio F AU - San Francisco IF AD - Departamento de Urologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile. FAU - Valenzuela, Rodrigo A AU - Valenzuela RA AD - Departamento de Ciencias Quimicas y Biologicas, Facultad de Salud, Universidad Bernardo O'Higgins, Santiago, Chile. FAU - Mendez, Gonzalo P AU - Mendez GP AD - Departamento de Anatomia Patologica, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile. FAU - Llanos, Carolina AU - Llanos C AD - Departamento de Inmunologia Clinica y Reumatologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191213 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Reactive Oxygen Species) RN - EC 1.14.14.18 (HMOX1 protein, human) RN - EC 1.14.14.18 (Heme Oxygenase-1) SB - IM MH - Adolescent MH - Adult MH - Female MH - Heme Oxygenase-1/*immunology MH - Humans MH - Kidney/immunology/pathology MH - Lupus Nephritis/*immunology/pathology MH - Male MH - Middle Aged MH - Monocytes/*immunology/pathology MH - *Phagocytosis MH - Reactive Oxygen Species/*immunology PMC - PMC6923251 OTO - NOTNLM OT - heme oxygenase-1 (HO-1) OT - lupus nephritis OT - monocytes OT - phagocytosis OT - reactive oxygen species (ROS) OT - renal biopsies EDAT- 2020/01/11 06:00 MHDA- 2020/11/05 06:00 PMCR- 2019/01/01 CRDT- 2020/01/11 06:00 PHST- 2019/05/30 00:00 [received] PHST- 2019/11/22 00:00 [accepted] PHST- 2020/01/11 06:00 [entrez] PHST- 2020/01/11 06:00 [pubmed] PHST- 2020/11/05 06:00 [medline] PHST- 2019/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2019.02868 [doi] PST - epublish SO - Front Immunol. 2019 Dec 13;10:2868. doi: 10.3389/fimmu.2019.02868. eCollection 2019.