Mast cells mediate acute kidney injury through the production of TNF

Shaun Andrew Summers, Jacky Chan, Poh-Yi Gan, Lakshi Dewage, Yuji Nozaki, Oliver Steinmetz, David Nikolic-Paterson, Arthur Kitching, Stephen Holdsworth

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)2226 - 2236
Number of pages11
JournalJournal of the American Society of Nephrology
Volume22
Issue number12
DOIs
Publication statusPublished - 2011

Cite this

Summers, Shaun Andrew ; Chan, Jacky ; Gan, Poh-Yi ; Dewage, Lakshi ; Nozaki, Yuji ; Steinmetz, Oliver ; Nikolic-Paterson, David ; Kitching, Arthur ; Holdsworth, Stephen. / Mast cells mediate acute kidney injury through the production of TNF. In: Journal of the American Society of Nephrology. 2011 ; Vol. 22, No. 12. pp. 2226 - 2236.
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title = "Mast cells mediate acute kidney injury through the production of TNF",
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.",
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Mast cells mediate acute kidney injury through the production of TNF. / Summers, Shaun Andrew; Chan, Jacky; Gan, Poh-Yi; Dewage, Lakshi; Nozaki, Yuji; Steinmetz, Oliver; Nikolic-Paterson, David; Kitching, Arthur; Holdsworth, Stephen.

In: Journal of the American Society of Nephrology, Vol. 22, No. 12, 2011, p. 2226 - 2236.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Summers, Shaun Andrew

AU - Chan, Jacky

AU - Gan, Poh-Yi

AU - Dewage, Lakshi

AU - Nozaki, Yuji

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AU - Nikolic-Paterson, David

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AU - Holdsworth, Stephen

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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.

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