Oxidized low-density lipoprotein antigen transport induces autoimmunity in the renal tubulointerstitium.

Abstract

BACKGROUND/AIMS:

Chronic kidney disease involves inflammation/oxidative stress, which contributes to progressive kidney injury.

METHODS:

Male Sprague-Dawley rats underwent 5/6 nephrectomy (Nx) or sham Nx and were sacrificed after 2 days, 2 weeks and 4 weeks. Microarray analysis expression sets over time suggested the evolution of renal lymphocyte infiltration and antigen-presenting cell (APC) activation after 5/6Nx. RT-PCR analysis also confirmed the migration and activation of lymphocytes and APCs through the upregulation of CD3, CXCR3/CXCL10 and CCR7/CCL19 mRNA in remnant kidney (RK). Purified T lymphocytes from spleen and unilateral ureteral obstruction (UUO) kidney were incubated with oxidized low-density lipoprotein (Ox-LDL)-treated major histocompatibility complex class II (MHC II)-expressing APCs. Culture supernatant was collected for mouse IFN-γ ELISA and cell proliferation was measured.

RESULTS:

Ox-LDL deposited predominantly in renal tubulointerstitial areas of RK, increased over time, and co-stained with lectin-like Ox-LDL receptor in affected renal tubular cells. Both Ox-LDL and renal-specific glycoprotein Tamm-Horsfall protein were identified in renal lymph nodes. Cells co-staining for major MHC II and Ox-LDL were observed in RK and draining renal lymph nodes after 5/6Nx. Similarly, Ox-LDL was also present in tubules after UUO, CD3-positive T cells were present in the interstitium, and Ox-LDL-treated MHC II-expressing APCs induced proliferation and IFN-γ production in renal tubulointerstitial T lymphocytes isolated from kidneys after UUO.

CONCLUSIONS:

These data demonstrate that the tubulointerstitial inflammatory infiltrate that accompanies chronic kidney disease reflects, at least in part, the development of autoimmunity to novel antigens generated during renal injury.

• Authors: Bancha Satirapoj, Kevin W Bruhn, Cynthia C Nast, Ying Wang, Tiane Dai, Janine Lapage, Xiwei Wu, Rama Natarajan, Sharon G Adler
• Journal: American journal of nephrology (Am J Nephrol) Vol. 35 Issue 6 Pg. 520-30 ( 2012) ISSN: 1421-9670 [Electronic] Switzerland
• PMID: 22653259 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 S. Karger AG, Basel.

Chemical References

• CCL19 protein, human
• CCR7 protein, human
• CD3 Complex
• CXCR3 protein, human
• Chemokine CCL19
• Chemokine CXCL10
• Histocompatibility Antigens Class II
• Lipoproteins, LDL
• OLR1 protein, rat
• RNA, Messenger
• Receptors, CCR7
• Receptors, CXCR3
• Scavenger Receptors, Class E
• Umod protein, rat
• Uromodulin
• oxidized low density lipoprotein
• Interferon-gamma

Topics

• Animals
• Autoimmunity
• CD3 Complex (metabolism)
• Cell Movement
• Cell Proliferation (drug effects)
• Cells, Cultured
• Chemokine CCL19 (metabolism)
• Chemokine CXCL10 (metabolism)
• Chronic Disease
• Histocompatibility Antigens Class II (metabolism)
• Interferon-gamma (drug effects, metabolism)
• Kidney Diseases (immunology, metabolism, pathology)
• Kidney Tubules (immunology, metabolism, pathology)
• Lipoproteins, LDL (immunology, pharmacology)
• Lymph Nodes (metabolism)
• Male
• Microarray Analysis
• Nephrectomy
• Nephritis, Interstitial (immunology, metabolism, pathology)
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, CCR7 (metabolism)
• Receptors, CXCR3 (metabolism)
• Scavenger Receptors, Class E (metabolism)
• T-Lymphocytes (metabolism, physiology)
• Ureteral Obstruction (immunology)
• Uromodulin (metabolism)