Involvement of endothelial cell adhesion molecules in the development of anti-Thy-1 nephritis.
To study an involvement of glomerular endothelial cells in the development of anti-Thy-1 nephritis, we examined the expression of endothelial cell adhesion molecules during the course of this model. Ribonuclease protection assay elucidated that expression of mRNA for intercellular adhesion molecule-1 (ICAM-1) was markedly enhanced in the glomeruli with a peak at 2 h (6.5-fold, p < 0.05) after the anti-Thy-1 antibody injection when mesangial cell lysis was recognized and IL-1beta mRNA expression was induced in the glomeruli. The glomerular ICAM-1 was predominantly localized in the endothelial cells and was intensely immunostained at day 1 in the glomerular endothelial cells. In contrast, platelet endothelial cell adhesion molecule-1 (PECAM-1) and vascular endothelial-cadherin mRNA expression increased gradually with a peak at day 6 (2.6-fold (p < 0.05) and 4.2-fold (p < 0.05), respectively) in the glomeruli with mesangial proliferative lesion. PECAM-1 was also immunolocalized in the glomerular endothelial cells and the immunoreactivity was greatly enhanced at day 6. Glomerular expression of vascular cell adhesion molecule-1 and endothelial leukocyte adhesion molecule-1 (E-selectin) was unchanged at a low level during the course of anti-Thy-1 nephritis. Blocking of ICAM-1 by administration of anti-ICAM-1 antibody showed significant decrease in the number of polymorphonuclear leukocytes accumulating in the glomeruli by 45.7% (9.4 +/- 0.2 vs. 5.1 +/- 0.1 per glomerular cross section, p < 0.01) at 2 h. These results suggest a significant involvement of glomerular endothelial cells in the development and repair of anti-Thy-1 nephritis via direct or indirect intercellular interactions between mesangial cells and glomerular endothelial cells.
Isome
Masato
M
Department of Structural Pathology, Institute of Nephrology, Faculty of Medicine, Niigata University, Niigata, Japan.
Fujinaka
Hidehiko
H
Yaoita
Eishin
E
Feng
Lili
L
Adhikary
Laxman P
LP
Abe
Akira
A
Tsuchida
Satoko
S
Kawasaki
Katsutoshi
K
Suzuki
Hitoshi
H
Kihara
Itaru
I
Wilson
Curtis B
CB
Yamamoto
Tadashi
T
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D004727:Endothelium / Q000378:metabolism; D005260:Female; D007158:Immunologic Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D007518:Isoantibodies / Q000276:immunology*; D007678:Kidney Glomerulus / Q000378:metabolism*; D009393:Nephritis / Q000276:immunology* / Q000652:urine; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology; D011507:Proteinuria / Q000209:etiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY
D000906:Antibodies; D015815:Cell Adhesion Molecules; D018836:Inflammation Mediators; D007518:Isoantibodies; D012333:RNA, Messenger; C035678:anti-Thy antibody; D018799:Intercellular Adhesion Molecule-1