Renal dendritic cells adopt a pro-inflammatory phenotype in obstructive uropathy to activate T cells but do not directly contribute to fibrosis

Sarah Snelgrove, Joshua Kausman, Cecilia Lo, Camden Lo, Joshua D Ooi, Patrick Coates, Michael Hickey, Stephen Holdsworth, Christian Kurts, Daniel Engel, Arthur Kitching

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Leukocyte recruitment contributes to acute kidney injury (AKI), but the mechanisms by which leukocytes promote injury are not completely understood. The degranulation of mast cells releases inflammatory molecules, including TNF, but whether these cells participate in the pathogenesis of AKI is unknown. Here, we induced AKI with cisplatin in mast cell-deficient and wild-type mice. Compared with wild-type mice, deficiency of mast cells attenuated renal injury, reduced serum levels of TNF, and reduced recruitment of leukocytes to the inflamed kidney. Mast cell-deficient mice also exhibited significantly lower intrarenal expression of leukocyte chemoattractants. Mast cell-deficient mice reconstituted with mast cells from wild-type mice exhibited similar cisplastin-induced renal damage and serum levels of TNF as wild-type mice. In contrast, mast cell-deficient mice reconstituted with mast cells from TNF-deficient mice continued to demonstrate significant attenuation of cisplatin-induced renal injury. Furthermore, the mast-cell stabilizer sodium chromoglycate also significantly abrogated renal injury in this model of AKI. Taken together, these results suggest that mast cells mediate AKI through the production of TNF.
Original languageEnglish
Pages (from-to)91 - 103
Number of pages13
JournalAmerican Journal of Pathology
Volume180
Issue number1
DOIs
Publication statusPublished - 2012

Cite this

@article{3d200a650d1e42b4b687824914f33c4c,
title = "Renal dendritic cells adopt a pro-inflammatory phenotype in obstructive uropathy to activate T cells but do not directly contribute to fibrosis",
abstract = "Leukocyte recruitment contributes to acute kidney injury (AKI), but the mechanisms by which leukocytes promote injury are not completely understood. The degranulation of mast cells releases inflammatory molecules, including TNF, but whether these cells participate in the pathogenesis of AKI is unknown. Here, we induced AKI with cisplatin in mast cell-deficient and wild-type mice. Compared with wild-type mice, deficiency of mast cells attenuated renal injury, reduced serum levels of TNF, and reduced recruitment of leukocytes to the inflamed kidney. Mast cell-deficient mice also exhibited significantly lower intrarenal expression of leukocyte chemoattractants. Mast cell-deficient mice reconstituted with mast cells from wild-type mice exhibited similar cisplastin-induced renal damage and serum levels of TNF as wild-type mice. In contrast, mast cell-deficient mice reconstituted with mast cells from TNF-deficient mice continued to demonstrate significant attenuation of cisplatin-induced renal injury. Furthermore, the mast-cell stabilizer sodium chromoglycate also significantly abrogated renal injury in this model of AKI. Taken together, these results suggest that mast cells mediate AKI through the production of TNF.",
author = "Sarah Snelgrove and Joshua Kausman and Cecilia Lo and Camden Lo and Ooi, {Joshua D} and Patrick Coates and Michael Hickey and Stephen Holdsworth and Christian Kurts and Daniel Engel and Arthur Kitching",
year = "2012",
doi = "10.1016/j.ajpath.2011.09.039",
language = "English",
volume = "180",
pages = "91 -- 103",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "American Society for Investigative Pathology",
number = "1",

}

Renal dendritic cells adopt a pro-inflammatory phenotype in obstructive uropathy to activate T cells but do not directly contribute to fibrosis. / Snelgrove, Sarah; Kausman, Joshua; Lo, Cecilia; Lo, Camden; Ooi, Joshua D; Coates, Patrick; Hickey, Michael; Holdsworth, Stephen; Kurts, Christian; Engel, Daniel; Kitching, Arthur.

In: American Journal of Pathology, Vol. 180, No. 1, 2012, p. 91 - 103.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Renal dendritic cells adopt a pro-inflammatory phenotype in obstructive uropathy to activate T cells but do not directly contribute to fibrosis

AU - Snelgrove, Sarah

AU - Kausman, Joshua

AU - Lo, Cecilia

AU - Lo, Camden

AU - Ooi, Joshua D

AU - Coates, Patrick

AU - Hickey, Michael

AU - Holdsworth, Stephen

AU - Kurts, Christian

AU - Engel, Daniel

AU - Kitching, Arthur

PY - 2012

Y1 - 2012

N2 - Leukocyte recruitment contributes to acute kidney injury (AKI), but the mechanisms by which leukocytes promote injury are not completely understood. The degranulation of mast cells releases inflammatory molecules, including TNF, but whether these cells participate in the pathogenesis of AKI is unknown. Here, we induced AKI with cisplatin in mast cell-deficient and wild-type mice. Compared with wild-type mice, deficiency of mast cells attenuated renal injury, reduced serum levels of TNF, and reduced recruitment of leukocytes to the inflamed kidney. Mast cell-deficient mice also exhibited significantly lower intrarenal expression of leukocyte chemoattractants. Mast cell-deficient mice reconstituted with mast cells from wild-type mice exhibited similar cisplastin-induced renal damage and serum levels of TNF as wild-type mice. In contrast, mast cell-deficient mice reconstituted with mast cells from TNF-deficient mice continued to demonstrate significant attenuation of cisplatin-induced renal injury. Furthermore, the mast-cell stabilizer sodium chromoglycate also significantly abrogated renal injury in this model of AKI. Taken together, these results suggest that mast cells mediate AKI through the production of TNF.

AB - Leukocyte recruitment contributes to acute kidney injury (AKI), but the mechanisms by which leukocytes promote injury are not completely understood. The degranulation of mast cells releases inflammatory molecules, including TNF, but whether these cells participate in the pathogenesis of AKI is unknown. Here, we induced AKI with cisplatin in mast cell-deficient and wild-type mice. Compared with wild-type mice, deficiency of mast cells attenuated renal injury, reduced serum levels of TNF, and reduced recruitment of leukocytes to the inflamed kidney. Mast cell-deficient mice also exhibited significantly lower intrarenal expression of leukocyte chemoattractants. Mast cell-deficient mice reconstituted with mast cells from wild-type mice exhibited similar cisplastin-induced renal damage and serum levels of TNF as wild-type mice. In contrast, mast cell-deficient mice reconstituted with mast cells from TNF-deficient mice continued to demonstrate significant attenuation of cisplatin-induced renal injury. Furthermore, the mast-cell stabilizer sodium chromoglycate also significantly abrogated renal injury in this model of AKI. Taken together, these results suggest that mast cells mediate AKI through the production of TNF.

UR - http://www.sciencedirect.com/science/article/pii/S0002944011009618

U2 - 10.1016/j.ajpath.2011.09.039

DO - 10.1016/j.ajpath.2011.09.039

M3 - Article

VL - 180

SP - 91

EP - 103

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 1

ER -