Lack of in vivo function of osteopontin in experimental anti-GBM nephritis.
Osteopontin (Opn) is a potent chemoattractant for mononuclear cells that is upregulated in various inflammatory states of the kidney. Opn is believed to contribute to mononuclear cell infiltration and renal injury. The importance of Opn was examined in vivo in rapidly progressive glomerulonephritis in Opn knockout mice. Glomerulonephritis was induced by intravenous injection of rabbit anti-mouse glomerular basement membrane antiserum in mice that had been presensitized to rabbit IgG. Immunologic responsiveness to rabbit IgG (assessed by cutaneous delayed-type hypersensitivity and antibody titers) showed no significant difference between wild-type and Opn -/- mice. Proteinuria was also similar in both groups. Glomerular crescent formation was not different in Opn +/+ and -/- groups (26 +/- 6% versus 29 +/- 7%). Tubulointerstitial infiltration was assessed qualitatively and showed no significant difference between the two genotypes. Formation of thrombi in the glomerular capillaries on a scale from 0 to 3 also showed no significant difference (1.3 +/- 0.3 for Opn +/+ and 1.4 +/- 0.3 for Opn -/- mice). Northern blot analysis of total kidney RNA showed a 5.1-fold increase of Opn expression in Opn +/+ mice compared with untreated controls and the absence of expression in Opn -/- mice, as expected. Regulated upon activation, normal T cell expressed and secreted (RANTES) and monocyte chemoattractant protein-1 mRNA levels were also markedly upregulated with no significant difference between the two strains, excluding compensatory overexpression of these two chemokines in Opn -/- mice. It is concluded that the known upregulation of Opn in murine anti-glomerular basement membrane nephritis does not significantly contribute to the glomerular and tubulointerstitial mononuclear cell infiltration in this model.
Bonvini
John Michael
JM
Institute of Physiology, University of Zürich, Switzerland.
Schatzmann
Ursula
U
Institute of Anatomy, University of Zürich, Switzerland.
Beck-Schimmer
Beatrice
B
Institute of Physiology, University of Zürich, Switzerland.
Sun
Li Kang
LK
Institute of Physiology, University of Zürich, Switzerland.
Rittling
Susan R
SR
Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey.
Denhardt
David T
DT
Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey.
LE Hir
Michel
M
Institute of Anatomy, University of Zürich, Switzerland.
Wüthrich
Rudolf P
RP
Institute of Physiology, University of Zürich, Switzerland.|Division of Nephrology, University Hospital, Zürich, Switzerland.
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000473:pathology / Q000503:physiopathology*; D000917:Antibody Formation / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects; D007074:Immunoglobulin G / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D053495:Osteopontin; D011817:Rabbits / Q000276:immunology; D012795:Sialoglycoproteins / Q000378:metabolism / Q000502:physiology*
D018925:Chemokines; D007074:Immunoglobulin G; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin