Effect of Heme Oxygenase-1 Depletion on Complement Regulatory Proteins Expression in the Rat

Heme oxygenase has been implicated in the regulation of various immune responses including complement activation. Using a transgenic rat model of HO-1 depletion, the present study assessed the effect of HO-1 absence on the expression of complement regulatory proteins: decay accelerating factor (DAF), CR1-related gene/protein Y (Crry) and CD59, which act to attenuate complement activation. Protein expression was assessed by immunohistochemistry in kidney, liver, lung and spleen tissues. DAF protein was reduced in all tissues retrieved from rats lacking HO-1 (Hmox1−/−) apart from spleen tissue sections. Crry protein was also reduced, but only in Hmox1−/− kidney and liver tissue. C3b staining was augmented in the kidney and spleen from Hmox1−/− rats, suggesting that the decrease of DAF and Crry was sufficient to increase C3b deposition. The observations support an important role of HO-1 as a regulator of the complement system.

[1]  Haifeng Zhang,et al.  C‐reactive protein inhibits C3a/C3aR‐dependent podocyte autophagy in favor of diabetic kidney disease , 2022, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[2]  E. Lianos,et al.  Regulation of Complement Activation by Heme Oxygenase-1 (HO-1) in Kidney Injury , 2021, Antioxidants.

[3]  V. D’Agati,et al.  Loss of decay-accelerating factor triggers podocyte injury and glomerulosclerosis , 2020, The Journal of experimental medicine.

[4]  P. Nilsson,et al.  The Role of Complement in Liver Injury, Regeneration, and Transplantation , 2019, Hepatology.

[5]  D. Tsiantoulas,et al.  Complement Factor H Modulates Splenic B Cell Development and Limits Autoantibody Production , 2019, Front. Immunol..

[6]  S. Miescher,et al.  Intravascular hemolysis activates complement via cell-free heme and heme-loaded microvesicles. , 2018, JCI insight.

[7]  A. Verkman,et al.  Complement regulator CD59 prevents peripheral organ injury in rats made seropositive for neuromyelitis optica immunoglobulin G , 2017, Acta Neuropathologica Communications.

[8]  E. Lianos,et al.  Phenotypic characterization of a novel HO-1 depletion model in the rat , 2017, Transgenic Research.

[9]  P. Duann,et al.  Heme Oxygenase 1 Up-Regulates Glomerular Decay Accelerating Factor Expression and Minimizes Complement Deposition and Injury. , 2016, The American journal of pathology.

[10]  A. Vlahou,et al.  Effect of Heme Oxygenase-1 Deficiency on Glomerular Proteomics , 2016, American Journal of Nephrology.

[11]  Xue-juan Li,et al.  The Expression Profile of Complement Components in Podocytes , 2016, International journal of molecular sciences.

[12]  V. Frémeaux-Bacchi,et al.  Complement System Part I – Molecular Mechanisms of Activation and Regulation , 2015, Front. Immunol..

[13]  M. Ruseva,et al.  Update on C3 glomerulopathy , 2014, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[14]  D. Wilkes,et al.  Complement system in lung disease. , 2014, American journal of respiratory cell and molecular biology.

[15]  S. Barnum,et al.  ICAM-1: Isoforms and Phenotypes , 2014, The Journal of Immunology.

[16]  A. Parsa,et al.  Complement anaphylatoxins as immune regulators in cancer , 2014, Cancer medicine.

[17]  K. Nath.  Heme oxygenase-1 and acute kidney injury , 2014, Current opinion in nephrology and hypertension.

[18]  N. Câmara,et al.  Cytoprotective role of heme oxygenase-1 and heme degradation derived end products in liver injury. , 2013, World journal of hepatology.

[19]  M. Mizuno,et al.  Specific collaboration between rat membrane complement regulators Crry and CD59 protects peritoneum from damage by autologous complement activation. , 2011, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[20]  L. Chau,et al.  Heme Oxygenase-1/Carbon Monoxide Induces Vascular Endothelial Growth Factor Expression via p38 Kinase-dependent Activation of Sp1* , 2010, The Journal of Biological Chemistry.

[21]  K. Pollard,et al.  Constitutive Expression of Murine Decay-Accelerating Factor 1 Is Controlled by the Transcription Factor Sp11 , 2006, The Journal of Immunology.

[22]  Ethanm . Shevach.  Complement , 2005 .

[23]  M. Čolić,et al.  The role of rat Crry, a complement regulatory protein, in proliferation of thymocytes. , 2004, Life sciences.

[24]  O. Spiller,et al.  Decay-accelerating factor expression in the rat kidney is restricted to the apical surface of podocytes. , 2002, Kidney international.

[25]  A. Frey,et al.  Expression of rat complement control protein Crry on tumor cells inhibits rat natural killer cell-mediated cytotoxicity. , 2002, Blood.

[26]  W. Song,et al.  Membrane complement regulatory proteins: insight from animal studies and relevance to human diseases. , 2001, International immunopharmacology.

[27]  O. Spiller,et al.  Human and rodent decay‐accelerating factors (CD55) are not species restricted in their complement‐inhibiting activities , 2000, Immunology.

[28]  H. Bonkovsky,et al.  Increased heme oxygenase‐1 gene expression in liver cells and splanchnic organs from portal hypertensive rats , 1999, Hepatology.

[29]  T. Hollmann,et al.  Cloning, expression, sequence determination, and chromosome localization of the mouse complement C3a anaphylatoxin receptor gene. , 1998, Molecular immunology.

[30]  G. Marilena,et al.  New physiological importance of two classic residual products: carbon monoxide and bilirubin. , 1997, Biochemical and molecular medicine.

[31]  M. Mizuno,et al.  Role of a rat membrane inhibitor of complement in anti-basement membrane antibody-induced renal injury. , 1995, Kidney international.

[32]  D. Kerjaschki,et al.  The Heymann nephritis antigenic complex: megalin (gp330) and RAP. , 1995, Journal of the American Society of Nephrology : JASN.

[33]  M. Kirschfink,et al.  The complement system in cancer: Ambivalence between tumour destruction and promotion. , 2017, Immunobiology.

[34]  S. A. Mitsialis,et al.  Heme Oxygenase-1 : A Multifaceted Triple-Threat Molecule The Role of Heme Oxygenase-1 in Pulmonary Disease , 2007 .