Preventive effect of sulphated colominic acid on P‐selectin‐dependent infiltration of macrophages in experimentally induced crescentic glomerulonephritis

Leucocytes infiltrate into renal tissue and are involved in the pathogenesis of crescentic glomerulonephritis. The initial event in the process of leucocyte infiltration is characterized by selectin‐mediated leucocyte rolling on endothelial surface. Role of selectins in pathogenesis of glomerulonephritis has still been controversial. Sulphated glycolipids and sulphated polysaccharides interfere with the binding of P‐ and L‐selectin with carbohydrate ligands on endothelial cells or on leucocytes. Here we evaluated the role of selectins and the preventive effects of sulphated colominic acid (SCA), a synthetic sulphated polysaccharide, on experimental crescentic glomerulonephritis in Wistar‐Kyoto (WKY) rats. Crescentic glomerulonephritis was induced by injection of nephrotoxic serum (NTS) in WKY rats. Rats subsequently received intraperitoneal injection of saline, neutralizing or non‐neutralizing monoclonal antibody (mAb) to rat P‐selectin and L‐selectin, SCA (5 or 10mg/kg/day) or nonsulphated colominic acid (CA) (10mg/kg/day) for 2 weeks. Localization of P‐, E‐selectin, ligands for L‐selectin and intraglomerular leucocytes was examined by immunohistochemistry. Gene expression of platelet‐derived growth factor (PDGF) B chain in glomeruli was quantified using real‐time RT‐PCR. P‐selectin was highly expressed on glomerular endothelial cells after injection of NTS, whereas E‐selectin and L‐selectin ligands were not detected. Anti‐P‐selectin mAb, but not anti‐L‐selectin mAb, significantly reduced glomerular infiltration of macrophages, crescent formation, and proteinuria. SCA also reduced proteinuria, macrophage infiltration, and crescent formation in a dose‐dependent manner. Furthermore, SCA suppressed gene expression of PDGF B chain in glomeruli. Our results indicate that P‐selectin partially mediate glomerular infiltration of macrophage in experimental crescentic glomerulonephritis. Moreover, SCA may inhibit intraglomerular infiltration of macrophages by interfering with P‐selectin‐dependent adhesion pathway, and progression of experimental crescentic glomerulonephritis.

[1]  N. Hotta,et al.  Effects of a new synthetic selectin blocker in an acute rat thrombotic glomerulonephritis. , 2001, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[2]  M. Haneda,et al.  Immunohistochemical characterization of glomerular PDGF B-chain and PDGF beta-receptor expression in diabetic rats. , 2000, Diabetes research and clinical practice.

[3]  P. Tipping,et al.  J Am Soc Nephrol 11: 262–269, 2000 Interleukin-10 Inhibits Macrophage-Induced Glomerular Injury , 2022 .

[4]  D. Loskutoff,et al.  Glomerular Extracellular Matrix Accumulation in Experimental Anti-GBM Ab Glomerulonephritis , 2000, Nephron.

[5]  R. Atkins,et al.  The role of selectins in glomerular leukocyte recruitment in rat anti-glomerular basement membrane glomerulonephritis. , 1999, Journal of the American Society of Nephrology : JASN.

[6]  H. Makino,et al.  L‐selectin and its ligands mediate infiltration of mononuclear cells into kidney interstitium after ureteric obstruction , 1999, The Journal of pathology.

[7]  W. Couser,et al.  Role of intrinsic renal cells versus infiltrating cells in glomerular crescent formation. , 1998, Kidney international.

[8]  P. Ward,et al.  In vitro and in vivo selectin-blocking activities of sulfated lipids and sulfated sialyl compounds. , 1998, International immunology.

[9]  F. Gejyo,et al.  Effects of a novel elastase inhibitor, ONO-5046, on nephrotoxic serum nephritis in rats. , 1998, Kidney international.

[10]  H. Makino,et al.  Increased expression of selectins in kidneys of patients with diabetic nephropathy , 1998, Diabetologia.

[11]  C. Alpers,et al.  A role for P-selectin in neutrophil and platelet infiltration in immune complex glomerulonephritis. , 1997, Journal of the American Society of Nephrology : JASN.

[12]  H. Makino,et al.  Increased Expression of Intercellular Adhesion Molecule-1 (ICAM-1) in Diabetic Rat Glomeruli: Glomerular Hyperfiltration Is a Potential Mechanism of ICAM-1 Upregulation , 1997, Diabetes.

[13]  T. Wada,et al.  In situ expression and soluble form of P-selectin in human glomerulonephritis. , 1997, Kidney international.

[14]  L. Feng,et al.  Crucial role of CD8-positive lymphocytes in glomerular expression of ICAM-1 and cytokines in crescentic glomerulonephritis of WKY rats. , 1997, Journal of immunology.

[15]  J. Lefkowith.  Leukocyte migration in immune complex glomerulonephritis: role of adhesion receptors. , 1997, Kidney international.

[16]  松田 充浩.  Glomerular Expression of Macrophage Colony-Stimulating Factor and Granulocyte-Macrophage Colony- Stimulating Factor in Patients with Various Forms of Glomerulonephritis , 1997 .

[17]  M. Hayashi,et al.  Role of P-selectin in the early stage of the Arthus reaction. , 1996, Immunopharmacology.

[18]  H. Makino,et al.  Glomerular expression of macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in patients with various forms of glomerulonephritis. , 1996, Laboratory investigation; a journal of technical methods and pathology.

[19]  J. Paulson,et al.  Reduction of rat myocardial ischemia and reperfusion injury by sialyl Lewis x oligosaccharide and anti-rat P-selectin antibodies. , 1996, Glycobiology.

[20]  H. Amagai,et al.  Sulfated colominic acid: an antiviral agent that inhibits the human immunodeficiency virus type 1 in vitro. , 1996, Antiviral research.

[21]  T. Mayadas,et al.  Acute passive anti-glomerular basement membrane nephritis in P-selectin-deficient mice. , 1996, Kidney international.

[22]  P. Ward,et al.  Anti-inflammatory effects of sulfatides in selectin-dependent acute lung injury. , 1995, International immunology.

[23]  T. Mayadas,et al.  Reduced recruitment of inflammatory cells in a contact hypersensitivity response in P-selectin-deficient mice , 1995, The Journal of experimental medicine.

[24]  H. Rennke,et al.  Transcellular biosynthesis of lipoxin A4 during adhesion of platelets and neutrophils in experimental immune complex glomerulonephritis. , 1995, Kidney international.

[25]  K. Ley,et al.  Lymphocyte homing and leukocyte rolling and migration are impaired in L-selectin-deficient mice. , 1994, Immunity.

[26]  P. Tipping,et al.  A role for P selectin in complement-independent neutrophil-mediated glomerular injury. , 1994, Kidney international.

[27]  T. Springer,et al.  Neutrophils roll on E-selectin. , 1993, Journal of immunology.

[28]  G. Schmid-Schönbein,et al.  Characterization of rat LECAM‐1 (L‐selectin) by the use of monoclonal antibodies and evidence for the presence of soluble LECAM‐1 in rat sera , 1993, European journal of immunology.

[29]  T. Mayadas,et al.  Leukocyte rolling and extravasation are severely compromised in P selectin-deficient mice , 1993, Cell.

[30]  C. Alpers,et al.  Role of platelet-derived growth factor in glomerular disease. , 1993, Journal of the American Society of Nephrology : JASN.

[31]  T. Watanabe,et al.  Molecular mechanisms underlying lymphocyte recirculation. III. Characterization of the LECAM-1 (L-selectin)-dependent adhesion pathway in rats. , 1993, Journal of immunology.

[32]  M. Sy,et al.  Antibodies to intercellular adhesion molecule 1/lymphocyte function- associated antigen 1 prevent crescent formation in rat autoimmune glomerulonephritis , 1993, The Journal of experimental medicine.

[33]  K. Kawasaki,et al.  Antibodies against intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 prevent glomerular injury in rat experimental crescentic glomerulonephritis. , 1993, Journal of immunology.

[34]  C. Smith,et al.  Requirements for leukocyte adhesion molecules in nephrotoxic nephritis. , 1993, The Journal of clinical investigation.

[35]  T. Watanabe,et al.  Sulfated glycolipids are ligands for a lymphocyte homing receptor, L-selectin (LECAM-1), Binding epitope in sulfated sugar chain. , 1993, Biochemical and biophysical research communications.

[36]  A. Aruffo,et al.  PMN binding to P‐selectin is inhibited by sulfatide , 1992, Journal of leukocyte biology.

[37]  C. Alpers,et al.  Demonstration of PDGF B-chain mRNA in glomeruli in mesangial proliferative nephritis by in situ hybridization. , 1991, Kidney international.

[38]  V. Cattell,et al.  Glomeruli synthesize nitrite in experimental nephrotoxic nephritis. , 1990, Kidney international.

[39]  S. Rosen,et al.  Direct demonstration of the lectin activity of gp90MEL, a lymphocyte homing receptor , 1990, The Journal of cell biology.

[40]  M. Miyasaka,et al.  Identification of monoclonal antibodies reactive with the rat homolog of ICAM-1, and evidence for a differential involvement of ICAM-1 in the adherence of resting versus activated lymphocytes to high endothelial cells. , 1990, International immunology.

[41]  H. Ushijima,et al.  Suppression of PrP(Sc)- and HIV-1 gp120 induced neuronal cell death by sulfated colominic acid. , 1999, Journal of neurovirology.

[42]  H. Makino,et al.  Gene expression of PDGF and PDGF receptor in various forms of glomerulonephritis. , 1997, American journal of nephrology.

[43]  T. Horiuchi,et al.  The critical role of intercellular adhesion molecule-1 in Masugi nephritis in rats. , 1996, Nephron.

[44]  H. Makino,et al.  Nephritogenicity of antibodies to proteoglycans of the glomerular basement membrane--I. , 1986, The Journal of clinical investigation.