BACKGROUND: This study evaluated the mechanisms of monocyte/macrophage (M/M) infiltration in a rat model of anti-glomerular basement membrane glomerulonephritis (GN). We focused on chemokines and osteopontin, which are known regulators of M/M recruitment. METHODS: Using immunohistology, in situ hybridization, and Northern blotting, the expression levels of chemokines and osteopontin were evaluated in isolated glomeruli and tubules 4, 10, and 20 days after the induction of GN. In vivo blocking experiments were performed by application of neutralizing antibodies against osteopontin and monocyte chemoattractant protein-1 (MCP-1). RESULTS: In nephritic animals, high glomerular MCP-1 and RANTES (regulated upon activation normal T cell expressed and secreted) expression levels were observed on days 4 and 10. The tubular expression of MCP-1, however, was only slightly enhanced. In contrast, tubular osteopontin production was maximally stimulated (day 10) and paralleled with peaks of albuminuria and tubulointerstitial M/M infiltration. Application of an anti-osteopontin antibody ameliorated tubulointerstitial and glomerular M/M recruitment, whereas treatment with an anti-MCP-1 antibody selectively reduced glomerular M/M recruitment. However, tubulointerstitial M/M infiltration remained unchanged. CONCLUSION: These studies show that chemokines and osteopontin are differentially expressed in glomeruli and tubules in this model of GN. Chemokines play a primary role in the glomeruli, whereas osteopontin has a predominant role in tubulointerstitial M/M recruitment. The roles of chemokines and osteopontin may thus be dependent on the renal compartment and on the disease model.
BACKGROUND: This study evaluated the mechanisms of monocyte/macrophage (M/M) infiltration in a rat model of anti-glomerular basement membrane glomerulonephritis (GN). We focused on chemokines and osteopontin, which are known regulators of M/M recruitment. METHODS: Using immunohistology, in situ hybridization, and Northern blotting, the expression levels of chemokines and osteopontin were evaluated in isolated glomeruli and tubules 4, 10, and 20 days after the induction of GN. In vivo blocking experiments were performed by application of neutralizing antibodies against osteopontin and monocyte chemoattractant protein-1 (MCP-1). RESULTS: In nephritic animals, high glomerular MCP-1 and RANTES (regulated upon activation normal T cell expressed and secreted) expression levels were observed on days 4 and 10. The tubular expression of MCP-1, however, was only slightly enhanced. In contrast, tubular osteopontin production was maximally stimulated (day 10) and paralleled with peaks of albuminuria and tubulointerstitial M/M infiltration. Application of an anti-osteopontin antibody ameliorated tubulointerstitial and glomerular M/M recruitment, whereas treatment with an anti-MCP-1 antibody selectively reduced glomerular M/M recruitment. However, tubulointerstitial M/M infiltration remained unchanged. CONCLUSION: These studies show that chemokines and osteopontin are differentially expressed in glomeruli and tubules in this model of GN. Chemokines play a primary role in the glomeruli, whereas osteopontin has a predominant role in tubulointerstitial M/M recruitment. The roles of chemokines and osteopontin may thus be dependent on the renal compartment and on the disease model.
Authors: Lina Wirestam; Helena Enocsson; Thomas Skogh; Leonid Padyukov; Andreas Jönsen; Murray B Urowitz; Dafna D Gladman; Juanita Romero-Diaz; Sang-Cheol Bae; Paul R Fortin; Jorge Sanchez-Guerrero; Ann E Clarke; Sasha Bernatsky; Caroline Gordon; John G Hanly; Daniel Wallace; David A Isenberg; Anisur Rahman; Joan Merrill; Ellen Ginzler; Graciela S Alarcón; W Winn Chatham; Michelle Petri; Munther Khamashta; Cynthia Aranow; Meggan Mackay; Mary Anne Dooley; Susan Manzi; Rosalind Ramsey-Goldman; Ola Nived; Kristjan Steinsson; Asad Zoma; Guillermo Ruiz-Irastorza; Sam Lim; Ken Kalunian; Murat Inanc; Ronald van Vollenhoven; Manuel Ramos-Casals; Diane L Kamen; Søren Jacobsen; Christine Peschken; Anca Askanase; Thomas Stoll; Ian N Bruce; Jonas Wetterö; Christopher Sjöwall Journal: J Rheumatol Date: 2019-01-15 Impact factor: 4.666
Authors: B S van der Veen; A H Petersen; J A Belperio; S C Satchell; P W Mathieson; G Molema; P Heeringa Journal: Clin Exp Immunol Date: 2009-10 Impact factor: 4.330