title: The Spleen Plays No Role in Nephrotoxic Serum Nephritis, but Constitutes a Place of Compensatory Haematopoiesis.
abstract: BACKGROUND
  The spleen has been implicated in the pathogenesis of immune-complex glomerulonephritis by initiating and resolving adaptive immune responses. Thus, we aimed to evaluate the role of the spleen in experimental nephrotoxic serum nephritis (NTS).
  
  
  METHODS
  In order to accelerate the disease, animals were subjected to NTS by preimmunizing male C57BL/6J mice with rabbit IgG three days before injecting the rabbit anti-glomerular basement antiserum, or were immunized only. A group underwent splenectomy before NTS induction.
  
  
  RESULTS
  We observed enlargement of the spleen with a maximum at 14 days after NTS induction or immunization only. Splenectomized mice were found to develop albuminuria and renal histological changes comparable to sham-operated controls. Nevertheless, anaemia was aggravated in mice after splenectomy. During the course of NTS, we detected CD41+ megakaryocytes and Ter119+ erythroid precursor cells in the spleen of mice with NTS and of immunized mice. Ter119+Cxcr4+ cells and the binding partner Cxcl12 increased in the spleen, and decreased in the bone marrow. This was accompanied by a significant systemic increase of interferon-gamma in the serum.
  
  
  CONCLUSIONS
  In summary, splenectomy does not influence the course of NTS per se, but is involved in concomitant anaemia. Extramedullary haematopoiesis in the spleen is probably facilitated through the migration of Cxcr4+ erythroid precursor cells from the bone marrow to the spleen via a Cxcl12 gradient and likely arises from the suppressive capacity of chronic inflammation on the bone marrow.
authors.affiliation: Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Artinger
authors.affiliation: Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Kirsch
authors.affiliation: Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Ida
authors.initials: I
authors.lastname: Aringer
authors.affiliation: Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Corinna
authors.initials: C
authors.lastname: Schabhüttl
authors.affiliation: Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Rosenkranz
authors.affiliation: Intensive Care Unit, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Eller
authors.affiliation: Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria; Clinical Division of Internal Medicine, Ospedale La Carità, Locarno, Switzerland.
authors.forename: Elena
authors.initials: E
authors.lastname: Rho
authors.affiliation: Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Eller
mesh_terms: D000419:Albuminuria / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000740:Anemia / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000818:Animals; D001789:Blood Group Antigens / Q000235:genetics / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D054377:Chemokine CXCL12 / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D006411:Hematopoiesis, Extramedullary / Q000276:immunology*; D007106:Immune Sera / Q000009:adverse effects; D007114:Immunization; D007074:Immunoglobulin G / Q000009:adverse effects; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D008297:Male; D008533:Megakaryocytes / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009393:Nephritis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D011817:Rabbits; D019718:Receptors, CXCR4 / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology* / Q000473:pathology; D013156:Splenectomy / Q000009:adverse effects*
chemical_list: D001789:Blood Group Antigens; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D007106:Immune Sera; D007074:Immunoglobulin G; D019718:Receptors, CXCR4; C489122:TER-119 antigen, mouse; D007371:Interferon-gamma