Therapeutic effects of prostacyclin analog on crescentic glomerulonephritis of rat

Masahiko Kushiro, Kenichi Shikata, Hikaru Sugimoto, Yasushi Shikata, Nobuyuki Miyatake, Jun Wada, Masayuki Miyasaka, Hirofumi Makino

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Prostacyclin (PGI2) is known to have a relaxative action on vascular smooth muscle, an inhibitory action against platelet activation and neutrophil function. Previous studies showed the preventive effects of PGI2 on lupus nephritis and Thy-1 nephritis, although the mechanism has not been clarified. Glomerular endothelial expression of intercellular adhesion molecule-1 (ICAM-1) is up-regulated in experimental and human glomerular diseases, and is known to facilitate leukocyte infiltration into the glomeruli, which ultimately induces the various glomerular injuries. In the present study, we evaluated the therapeutic effects of PGI2 on a rat model for crescentic glomerulonephritis and investigated its putative mechanism in relation to ICAM-1-mediated leukocyte recruitment. Wistar-Kyoto (WKY) rats were injected with nephrotoxic serum and received continuous intraperitoneal infusion of PGI2. PGI2 dramatically decreased proteinuria (123.0 ± 18.8 vs. 31.6 ± 4.5), crescent formation and deposition of fibrinogen in the glomeruli, while the deposition of rabbit IgG, rat IgG and rat C3 along the capillary walls was not changed. Furthermore, intraglomerular expression of ICAM-1 and infiltration of macrophages were significantly suppressed by administration with PGI2. In contrast, influx of CD4 or CD8 positive cells was not altered. The present results suggest that PGI2 shows the preventive effects on experimental crescentic glomerulonephritis by inhibiting intraglomerular coagulation and ICAM-1-mediated macrophage-glomerular endothelial cell adhesive pathway.

Original languageEnglish
Pages (from-to)1314-1320
Number of pages7
JournalKidney International
Volume53
Issue number5
DOIs
Publication statusPublished - 1998
Externally publishedYes

Fingerprint

Therapeutic Uses
Epoprostenol
Glomerulonephritis
Intercellular Adhesion Molecule-1
Leukocytes
Immunoglobulin G
Macrophages
Parenteral Infusions
Lupus Nephritis
Inbred WKY Rats
Nephritis
Platelet Activation
Vascular Smooth Muscle
Proteinuria
Adhesives
Fibrinogen
Neutrophils
Endothelial Cells
Rabbits
Wounds and Injuries

Keywords

  • Fibrinogen
  • ICAM-1
  • Intraglomerular coagulation
  • Leukocyte recruitment
  • Macrophages

ASJC Scopus subject areas

  • Nephrology

Cite this

Therapeutic effects of prostacyclin analog on crescentic glomerulonephritis of rat. / Kushiro, Masahiko; Shikata, Kenichi; Sugimoto, Hikaru; Shikata, Yasushi; Miyatake, Nobuyuki; Wada, Jun; Miyasaka, Masayuki; Makino, Hirofumi.

In: Kidney International, Vol. 53, No. 5, 1998, p. 1314-1320.

Research output: Contribution to journalArticle

Kushiro, Masahiko ; Shikata, Kenichi ; Sugimoto, Hikaru ; Shikata, Yasushi ; Miyatake, Nobuyuki ; Wada, Jun ; Miyasaka, Masayuki ; Makino, Hirofumi. / Therapeutic effects of prostacyclin analog on crescentic glomerulonephritis of rat. In: Kidney International. 1998 ; Vol. 53, No. 5. pp. 1314-1320.
@article{d017368091f748b08733ce387f06c7b9,
title = "Therapeutic effects of prostacyclin analog on crescentic glomerulonephritis of rat",
abstract = "Prostacyclin (PGI2) is known to have a relaxative action on vascular smooth muscle, an inhibitory action against platelet activation and neutrophil function. Previous studies showed the preventive effects of PGI2 on lupus nephritis and Thy-1 nephritis, although the mechanism has not been clarified. Glomerular endothelial expression of intercellular adhesion molecule-1 (ICAM-1) is up-regulated in experimental and human glomerular diseases, and is known to facilitate leukocyte infiltration into the glomeruli, which ultimately induces the various glomerular injuries. In the present study, we evaluated the therapeutic effects of PGI2 on a rat model for crescentic glomerulonephritis and investigated its putative mechanism in relation to ICAM-1-mediated leukocyte recruitment. Wistar-Kyoto (WKY) rats were injected with nephrotoxic serum and received continuous intraperitoneal infusion of PGI2. PGI2 dramatically decreased proteinuria (123.0 ± 18.8 vs. 31.6 ± 4.5), crescent formation and deposition of fibrinogen in the glomeruli, while the deposition of rabbit IgG, rat IgG and rat C3 along the capillary walls was not changed. Furthermore, intraglomerular expression of ICAM-1 and infiltration of macrophages were significantly suppressed by administration with PGI2. In contrast, influx of CD4 or CD8 positive cells was not altered. The present results suggest that PGI2 shows the preventive effects on experimental crescentic glomerulonephritis by inhibiting intraglomerular coagulation and ICAM-1-mediated macrophage-glomerular endothelial cell adhesive pathway.",
keywords = "Fibrinogen, ICAM-1, Intraglomerular coagulation, Leukocyte recruitment, Macrophages",
author = "Masahiko Kushiro and Kenichi Shikata and Hikaru Sugimoto and Yasushi Shikata and Nobuyuki Miyatake and Jun Wada and Masayuki Miyasaka and Hirofumi Makino",
year = "1998",
doi = "10.1046/j.1523-1755.1998.00881.x",
language = "English",
volume = "53",
pages = "1314--1320",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Therapeutic effects of prostacyclin analog on crescentic glomerulonephritis of rat

AU - Kushiro, Masahiko

AU - Shikata, Kenichi

AU - Sugimoto, Hikaru

AU - Shikata, Yasushi

AU - Miyatake, Nobuyuki

AU - Wada, Jun

AU - Miyasaka, Masayuki

AU - Makino, Hirofumi

PY - 1998

Y1 - 1998

N2 - Prostacyclin (PGI2) is known to have a relaxative action on vascular smooth muscle, an inhibitory action against platelet activation and neutrophil function. Previous studies showed the preventive effects of PGI2 on lupus nephritis and Thy-1 nephritis, although the mechanism has not been clarified. Glomerular endothelial expression of intercellular adhesion molecule-1 (ICAM-1) is up-regulated in experimental and human glomerular diseases, and is known to facilitate leukocyte infiltration into the glomeruli, which ultimately induces the various glomerular injuries. In the present study, we evaluated the therapeutic effects of PGI2 on a rat model for crescentic glomerulonephritis and investigated its putative mechanism in relation to ICAM-1-mediated leukocyte recruitment. Wistar-Kyoto (WKY) rats were injected with nephrotoxic serum and received continuous intraperitoneal infusion of PGI2. PGI2 dramatically decreased proteinuria (123.0 ± 18.8 vs. 31.6 ± 4.5), crescent formation and deposition of fibrinogen in the glomeruli, while the deposition of rabbit IgG, rat IgG and rat C3 along the capillary walls was not changed. Furthermore, intraglomerular expression of ICAM-1 and infiltration of macrophages were significantly suppressed by administration with PGI2. In contrast, influx of CD4 or CD8 positive cells was not altered. The present results suggest that PGI2 shows the preventive effects on experimental crescentic glomerulonephritis by inhibiting intraglomerular coagulation and ICAM-1-mediated macrophage-glomerular endothelial cell adhesive pathway.

AB - Prostacyclin (PGI2) is known to have a relaxative action on vascular smooth muscle, an inhibitory action against platelet activation and neutrophil function. Previous studies showed the preventive effects of PGI2 on lupus nephritis and Thy-1 nephritis, although the mechanism has not been clarified. Glomerular endothelial expression of intercellular adhesion molecule-1 (ICAM-1) is up-regulated in experimental and human glomerular diseases, and is known to facilitate leukocyte infiltration into the glomeruli, which ultimately induces the various glomerular injuries. In the present study, we evaluated the therapeutic effects of PGI2 on a rat model for crescentic glomerulonephritis and investigated its putative mechanism in relation to ICAM-1-mediated leukocyte recruitment. Wistar-Kyoto (WKY) rats were injected with nephrotoxic serum and received continuous intraperitoneal infusion of PGI2. PGI2 dramatically decreased proteinuria (123.0 ± 18.8 vs. 31.6 ± 4.5), crescent formation and deposition of fibrinogen in the glomeruli, while the deposition of rabbit IgG, rat IgG and rat C3 along the capillary walls was not changed. Furthermore, intraglomerular expression of ICAM-1 and infiltration of macrophages were significantly suppressed by administration with PGI2. In contrast, influx of CD4 or CD8 positive cells was not altered. The present results suggest that PGI2 shows the preventive effects on experimental crescentic glomerulonephritis by inhibiting intraglomerular coagulation and ICAM-1-mediated macrophage-glomerular endothelial cell adhesive pathway.

KW - Fibrinogen

KW - ICAM-1

KW - Intraglomerular coagulation

KW - Leukocyte recruitment

KW - Macrophages

UR - http://www.scopus.com/inward/record.url?scp=0031820562&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031820562&partnerID=8YFLogxK

U2 - 10.1046/j.1523-1755.1998.00881.x

DO - 10.1046/j.1523-1755.1998.00881.x

M3 - Article

VL - 53

SP - 1314

EP - 1320

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 5

ER -