Effects of a specific thromboxane synthetase inhibitor on development of experimental Dirofilaria immitis immune complex glomerulonephritis in the dog.
Twelve Beagle dogs were immunized with aqueous-soluble Dirofilaria immitis antigens, and subsequent to at least fivefold increases in serum antibody titer, 6 mg of homologous antigen was infused into the left renal artery. Six dogs were treated once daily starting the day of infusion with 0.75 mg/kg of 1-benzylimidazole (1-BIM) in saline. Six control dogs were given saline only. Light, immunofluorescent, and transmission electron microscopic examinations of renal tissue from control dogs, 10 days after antigen infusion, showed a mesangioproliferative glomerulonephritis in the left kidney with polymorphonuclear leukocyte (PMNL) infiltration and fibrin deposition. Immunoglobulin (Ig) G, M, C3, and Dirofilaria antigen deposits were observed in a segmental granular pattern. Mesangial, subendothelial, and intramembranous electron dense deposits were observed, and anti-Dirofilaria antibodies were demonstrated in kidney eluates from each dog. Administration of 1-BIM had no significant effect on IgG, IgM, C3, or antigen deposits, electron dense deposits, or concentration of antibody in kidney eluates. However, 1-BIM-treated dogs had less glomerular cell proliferation, periodic acid-Schiff (PAS) positive glomerular staining, PMNL infiltration, and fibrin deposition. These data suggest that thromboxane is an important mediator in the development of immune complex glomerulonephritis, and that in certain circumstances, inhibition of thromboxane synthesis may be an effective therapy for immune complex glomerulonephritis in the dog.
Grauer
G F
GF
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison 53706.
Culham
C A
CA
Dubielzig
R R
RR
Presto
S K
SK
Oberley
T D
TD
Thomas
C B
CB
Grieve
R B
RB
D000818:Animals; D000909:Antibodies, Helminth / Q000032:analysis; D000947:Antigens, Helminth / Q000032:analysis / Q000276:immunology; D004183:Dirofilaria immitis / Q000254:growth & development / Q000276:immunology*; D004283:Dog Diseases / Q000188:drug therapy* / Q000276:immunology; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D005260:Female; D005370:Filarioidea / Q000276:immunology*; D005921:Glomerulonephritis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000662:veterinary*; D007093:Imidazoles / Q000627:therapeutic use*; D007105:Immune Complex Diseases / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000662:veterinary*; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D007093:Imidazoles; C017062:1-benzylimidazole; D013930:Thromboxane-A Synthase