Attenuation of folic acid-induced renal inflammatory injury in platelet-activating factor receptor-deficient mice

Kent Doi, Koji Okamoto, Kousuke Negishi, Yoshifumi Suzuki, Akihide Nakao, Toshiro Fujita, Akiko Toda, Takehiko Yokomizo, Yoshihiro Kita, Yasuyuki Kihara, Satoshi Ishii, Takao Shimizu, Eisei Noiri

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)

Abstract

Platelet-activating factor (PAF), a potent lipid mediator with various biological activities, plays an important role in inflammation by recruiting leukocytes. In this study we used platelet-activating factor receptor (PAFR)-deficient mice to elucidate the role of PAF in inflammatory renal injury induced by fblic acid administration. PAFR-deficient mice showed significant amelioration of renal dysfunction and pathological findings such as acute tubular damage with neutrophil infiltration, lipid peroxidation observed with antibody to 4-hydroxy-2-hexenal (day 2), and interstitial fibrosis with macrophage infiltration associated with expression of monocyte chemoattractant protein-1 and tumor necrosis factor-α in the kidney (day 14). Acute tubular damage was attenuated by neutrophil depletion using a monoclonal antibody (RB6-8C5), demonstrating the contribution of neutrophils to acute phase injury. Macrophage infiltration was also decreased when treatment with a PAJF antagonist (WEB2086) was started after acute phase. In vitro chemotaxis assay using a Boyden chamber demonstrated that PAF exhibits a strong chemotactic activity for macrophages. These results indicate that PAF is involved in pathogenesis of fblic acid-induced renal injury by activating neutrophils in acute phase and macrophages in chronic interstitial fibrosis. Inhibiting the PAF pathway might be therapeutic to kidney injury from inflammatory cells.

Original languageEnglish
Pages (from-to)1413-1424
Number of pages12
JournalAmerican Journal of Pathology
Volume168
Issue number5
DOIs
Publication statusPublished - 2006 May
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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