期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 170, 期 2, 页码 526-537出版社
ELSEVIER SCIENCE INC
DOI: 10.2353/ajpath.2007.060366
关键词
-
类别
资金
- NIAID NIH HHS [R01 AI024431, U01 AI054782, U54 AI057168] Funding Source: Medline
Neutrophilia is a characteristic of hemolytic uremic syndrome caused by Shiga toxin (Stx2)-producing Escherichia coli. However, the role of neutrophils in the toxin-induced renal injury occurring in enterohemorrhagic E. coli infection remains undefined. We report the trafficking of nentrophils to the kidney of C57BL/6 mice throughout a 72-hour time course after challenge with purified E. coli Stx2 and lipopolysaccharide (LPS). Increased neutrophils were observed in the renal cortex, particularly within the glomeruli where a more than fourfold increase in neutrophils was noted within 2 hours after challenge. Using microarray analysis, an increased number of transcripts for chemoattractants CXCL1/KC (69-fold at 2 hours) and CXCL2/MIP-2 (29-fold at 2 hours) were detected. Ribomiclease protection assays, Northern blotting, enzyme-linked immunosorbent assay, and immunohistochemistry confirmed microarray results, showing that both chemokines were expressed only on the immediate periglomerular epithelium and that these events coincided with neutrophil invasion of glomeruli. Co-administration of Stx2 with LPS enhanced and prolonged the KC and MIP-2 host response (RNA and protein) induced by LPS alone. Immunoneutralization in vivo of CXCL1/KC and CXCL2/MIP-2 abrogated neutrophil migration into glomeruli by 85%. These data define the molecular basis for neutrophil migration into the kidney after exposure to virulence factors of Shigatoxin-producing E. coli O157:H7.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据