Serum autoantibodies in pristane induced lupus are regulated by neutrophil gelatinase associated lipocalin

Rahul D. Pawar; Beatrice Goilav; Yumin Xia; Haoyang Zhuang; Leal Herlitz; Westley H. Reeves; Chaim Putterman

doi:10.1016/j.clim.2014.06.007

Serum autoantibodies in pristane induced lupus are regulated by neutrophil gelatinase associated lipocalin

Rahul D. Pawar, Beatrice Goilav, Yumin Xia, Haoyang Zhuang, Leal Herlitz, Westley H. Reeves, Chaim Putterman

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19 Scopus citations

Abstract

The onset of autoantibodies in systemic autoimmunity can be the result of a breakdown in tolerance at multiple checkpoints. Genetic, hormonal, and immunological factors can combine with environmental influences to accelerate the onset of disease and aggravate disease outcome. Here, we describe a novel mechanism relating to the regulatory role of Neutrophil Gelatinase Associated Lipocalin (NGAL) in modulating the levels of autoantibodies in pristane induced lupus. Following a single injection of pristane intraperitoneally, NGAL expression was induced in both the serum and spleen. Furthermore, NGAL deficient mice were more susceptible to the induction of pristane stimulated autoimmunity, and displayed higher numbers of autoantibody secreting cells and increased expression of activation induced cytidine deaminase (AID) and other inflammatory mediators in the spleen. In contrast, kidney damage was milder in NGAL deficient mice, indicating that NGAL was detrimental in autoantibody mediated kidney disease. These studies indicate that NGAL plays differential roles in different tissues in the context of lupus, and suggest a previously unrecognized role for NGAL in adaptive immunity.

Original language	English
Pages (from-to)	49-65
Number of pages	17
Journal	Clinical Immunology
Volume	154
Issue number	1
DOIs	https://doi.org/10.1016/j.clim.2014.06.007
State	Published - Sep 2014
Externally published	Yes

Bibliographical note

Funding Information:
This study was supported by grants from the −/− mice. The authors would like to acknowledge the laboratory of Dr. Richard Stanley (Albert Einstein College of Medicine) for their help in macrophage isolation. NIH RO1-AR048692 and RO1-DK090319 (to C.P.) and an Arthritis Foundation fellowship (# 5451 ) (to R.D.P.). Westley H. Reeves and Haoyang Zhuang were supported by grants RO1-AR44731 and T32AR007603 respectively. The authors thank Drs. Thorsten Berger and Tak W. Mak (Ontario Cancer Institute, Canada) for generously providing the NGAL

Funding

This study was supported by grants from the −/− mice. The authors would like to acknowledge the laboratory of Dr. Richard Stanley (Albert Einstein College of Medicine) for their help in macrophage isolation. NIH RO1-AR048692 and RO1-DK090319 (to C.P.) and an Arthritis Foundation fellowship (# 5451 ) (to R.D.P.). Westley H. Reeves and Haoyang Zhuang were supported by grants RO1-AR44731 and T32AR007603 respectively. The authors thank Drs. Thorsten Berger and Tak W. Mak (Ontario Cancer Institute, Canada) for generously providing the NGAL

Funders	Funder number
National Institutes of Health	RO1-AR048692
National Institute of Diabetes and Digestive and Kidney Diseases	R01DK090319
Arthritis Foundation	5451, T32AR007603, RO1-AR44731

Keywords

Autoantibodies
Lipocalin-2
NGAL
Pristane
SLE

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title = "Serum autoantibodies in pristane induced lupus are regulated by neutrophil gelatinase associated lipocalin",

abstract = "The onset of autoantibodies in systemic autoimmunity can be the result of a breakdown in tolerance at multiple checkpoints. Genetic, hormonal, and immunological factors can combine with environmental influences to accelerate the onset of disease and aggravate disease outcome. Here, we describe a novel mechanism relating to the regulatory role of Neutrophil Gelatinase Associated Lipocalin (NGAL) in modulating the levels of autoantibodies in pristane induced lupus. Following a single injection of pristane intraperitoneally, NGAL expression was induced in both the serum and spleen. Furthermore, NGAL deficient mice were more susceptible to the induction of pristane stimulated autoimmunity, and displayed higher numbers of autoantibody secreting cells and increased expression of activation induced cytidine deaminase (AID) and other inflammatory mediators in the spleen. In contrast, kidney damage was milder in NGAL deficient mice, indicating that NGAL was detrimental in autoantibody mediated kidney disease. These studies indicate that NGAL plays differential roles in different tissues in the context of lupus, and suggest a previously unrecognized role for NGAL in adaptive immunity.",

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author = "Pawar, {Rahul D.} and Beatrice Goilav and Yumin Xia and Haoyang Zhuang and Leal Herlitz and Reeves, {Westley H.} and Chaim Putterman",

note = "Funding Information: This study was supported by grants from the −/− mice. The authors would like to acknowledge the laboratory of Dr. Richard Stanley (Albert Einstein College of Medicine) for their help in macrophage isolation. NIH RO1-AR048692 and RO1-DK090319 (to C.P.) and an Arthritis Foundation fellowship (# 5451 ) (to R.D.P.). Westley H. Reeves and Haoyang Zhuang were supported by grants RO1-AR44731 and T32AR007603 respectively. The authors thank Drs. Thorsten Berger and Tak W. Mak (Ontario Cancer Institute, Canada) for generously providing the NGAL",

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N2 - The onset of autoantibodies in systemic autoimmunity can be the result of a breakdown in tolerance at multiple checkpoints. Genetic, hormonal, and immunological factors can combine with environmental influences to accelerate the onset of disease and aggravate disease outcome. Here, we describe a novel mechanism relating to the regulatory role of Neutrophil Gelatinase Associated Lipocalin (NGAL) in modulating the levels of autoantibodies in pristane induced lupus. Following a single injection of pristane intraperitoneally, NGAL expression was induced in both the serum and spleen. Furthermore, NGAL deficient mice were more susceptible to the induction of pristane stimulated autoimmunity, and displayed higher numbers of autoantibody secreting cells and increased expression of activation induced cytidine deaminase (AID) and other inflammatory mediators in the spleen. In contrast, kidney damage was milder in NGAL deficient mice, indicating that NGAL was detrimental in autoantibody mediated kidney disease. These studies indicate that NGAL plays differential roles in different tissues in the context of lupus, and suggest a previously unrecognized role for NGAL in adaptive immunity.

AB - The onset of autoantibodies in systemic autoimmunity can be the result of a breakdown in tolerance at multiple checkpoints. Genetic, hormonal, and immunological factors can combine with environmental influences to accelerate the onset of disease and aggravate disease outcome. Here, we describe a novel mechanism relating to the regulatory role of Neutrophil Gelatinase Associated Lipocalin (NGAL) in modulating the levels of autoantibodies in pristane induced lupus. Following a single injection of pristane intraperitoneally, NGAL expression was induced in both the serum and spleen. Furthermore, NGAL deficient mice were more susceptible to the induction of pristane stimulated autoimmunity, and displayed higher numbers of autoantibody secreting cells and increased expression of activation induced cytidine deaminase (AID) and other inflammatory mediators in the spleen. In contrast, kidney damage was milder in NGAL deficient mice, indicating that NGAL was detrimental in autoantibody mediated kidney disease. These studies indicate that NGAL plays differential roles in different tissues in the context of lupus, and suggest a previously unrecognized role for NGAL in adaptive immunity.

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Serum autoantibodies in pristane induced lupus are regulated by neutrophil gelatinase associated lipocalin

Abstract

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Keywords

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