The long pentraxin PTX3 is an endogenous inhibitor of hyperoxaluria-related nephrocalcinosis and chronic kidney disease

Julia A. Marschner, Shrikant R. Mulay, Stefanie Steiger, Lidia Anguiano, Zhibo Zhao, Peter Boor, Khosrow Rahimi, Antonio Inforzato, Cecilia Garlanda, Alberto Mantovani, Hans Joachim Anders

Research output: Contribution to journalArticle

Abstract

The long pentraxin 3 (PTX3) exerts a variety of regulatory functions in acute and chronic tissue inflammation. In particular, PTX3 acts as an opsonin for a variety of pathogens and endogenous particles. We hypothesized that PTX3 would exhibit opsonin-like functions toward calcium oxalate crystals, too, and inhibit crystal growth. This process is fundamental in kidney stone disease as well as in hyperoxaluria-related nephrocalcinosis, the paradigmatic cause of chronic kidney disease (CKD) in children with primary hyperoxaluria type I due to genetic defects in oxalate metabolism. Direct effects of PTX3 on calcium oxalate crystals were investigated in chemico by adding recombinant PTX3 to supersaturated calcium and oxalate solutions. PTX3, but not isomolar concentrations of albumin, dose-dependently inhibited crystal growth. In vivo, the PTX3 protein was undetectable in tubular epithelial cells and urine of wild-type mice under physiological conditions. However, its levels increased within 3 weeks of feeding an oxalate-rich diet, an exposure inducing hyperoxaluria-related nephrocalcinosis and CKD in selected mouse strains (male and female C57BL/6N and male Balb/c mice) but not in others (male and female 129SV and CD-1, male and female Balb/c mice). Genetic ablation of ptx3 in nephrocalcinosis un-susceptible B6;129 mice was sufficient to raise the oxalate nephropathy phenotype observed in susceptible strains. We conclude that PTX3 is an endogenous inhibitor of calcium oxalate crystal growth. This mechanism limits hyperoxaluria-related nephrocalcinosis, e.g., in primary or secondary hyperoxaluria, and potentially also in the more prevalent kidney stone disease.

Original languageEnglish
Article number2173
JournalFrontiers in Immunology
Volume9
Issue numberSEP
DOIs
Publication statusPublished - Sep 25 2018

Fingerprint

Hyperoxaluria
Nephrocalcinosis
Chronic Renal Insufficiency
Calcium Oxalate
Oxalates
Opsonin Proteins
Kidney Calculi
Kidney Diseases
Crystallization
129 Strain Mouse
PTX3 protein
Albumins
Epithelial Cells
Urine
Diet
Inflammation
Phenotype

Keywords

  • Colic
  • Crystals
  • Hyperoxaluria
  • Kidney stone
  • Nephrolithiasis
  • PTX3
  • Urolithiasis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Marschner, J. A., Mulay, S. R., Steiger, S., Anguiano, L., Zhao, Z., Boor, P., ... Anders, H. J. (2018). The long pentraxin PTX3 is an endogenous inhibitor of hyperoxaluria-related nephrocalcinosis and chronic kidney disease. Frontiers in Immunology, 9(SEP), [2173]. https://doi.org/10.3389/fimmu.2018.02173

The long pentraxin PTX3 is an endogenous inhibitor of hyperoxaluria-related nephrocalcinosis and chronic kidney disease. / Marschner, Julia A.; Mulay, Shrikant R.; Steiger, Stefanie; Anguiano, Lidia; Zhao, Zhibo; Boor, Peter; Rahimi, Khosrow; Inforzato, Antonio; Garlanda, Cecilia; Mantovani, Alberto; Anders, Hans Joachim.

In: Frontiers in Immunology, Vol. 9, No. SEP, 2173, 25.09.2018.

Research output: Contribution to journalArticle

Marschner, Julia A. ; Mulay, Shrikant R. ; Steiger, Stefanie ; Anguiano, Lidia ; Zhao, Zhibo ; Boor, Peter ; Rahimi, Khosrow ; Inforzato, Antonio ; Garlanda, Cecilia ; Mantovani, Alberto ; Anders, Hans Joachim. / The long pentraxin PTX3 is an endogenous inhibitor of hyperoxaluria-related nephrocalcinosis and chronic kidney disease. In: Frontiers in Immunology. 2018 ; Vol. 9, No. SEP.
@article{1c7aea809a9c44dabde4141f473ea1b3,
title = "The long pentraxin PTX3 is an endogenous inhibitor of hyperoxaluria-related nephrocalcinosis and chronic kidney disease",
abstract = "The long pentraxin 3 (PTX3) exerts a variety of regulatory functions in acute and chronic tissue inflammation. In particular, PTX3 acts as an opsonin for a variety of pathogens and endogenous particles. We hypothesized that PTX3 would exhibit opsonin-like functions toward calcium oxalate crystals, too, and inhibit crystal growth. This process is fundamental in kidney stone disease as well as in hyperoxaluria-related nephrocalcinosis, the paradigmatic cause of chronic kidney disease (CKD) in children with primary hyperoxaluria type I due to genetic defects in oxalate metabolism. Direct effects of PTX3 on calcium oxalate crystals were investigated in chemico by adding recombinant PTX3 to supersaturated calcium and oxalate solutions. PTX3, but not isomolar concentrations of albumin, dose-dependently inhibited crystal growth. In vivo, the PTX3 protein was undetectable in tubular epithelial cells and urine of wild-type mice under physiological conditions. However, its levels increased within 3 weeks of feeding an oxalate-rich diet, an exposure inducing hyperoxaluria-related nephrocalcinosis and CKD in selected mouse strains (male and female C57BL/6N and male Balb/c mice) but not in others (male and female 129SV and CD-1, male and female Balb/c mice). Genetic ablation of ptx3 in nephrocalcinosis un-susceptible B6;129 mice was sufficient to raise the oxalate nephropathy phenotype observed in susceptible strains. We conclude that PTX3 is an endogenous inhibitor of calcium oxalate crystal growth. This mechanism limits hyperoxaluria-related nephrocalcinosis, e.g., in primary or secondary hyperoxaluria, and potentially also in the more prevalent kidney stone disease.",
keywords = "Colic, Crystals, Hyperoxaluria, Kidney stone, Nephrolithiasis, PTX3, Urolithiasis",
author = "Marschner, {Julia A.} and Mulay, {Shrikant R.} and Stefanie Steiger and Lidia Anguiano and Zhibo Zhao and Peter Boor and Khosrow Rahimi and Antonio Inforzato and Cecilia Garlanda and Alberto Mantovani and Anders, {Hans Joachim}",
year = "2018",
month = "9",
day = "25",
doi = "10.3389/fimmu.2018.02173",
language = "English",
volume = "9",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S.A.",
number = "SEP",

}

TY - JOUR

T1 - The long pentraxin PTX3 is an endogenous inhibitor of hyperoxaluria-related nephrocalcinosis and chronic kidney disease

AU - Marschner, Julia A.

AU - Mulay, Shrikant R.

AU - Steiger, Stefanie

AU - Anguiano, Lidia

AU - Zhao, Zhibo

AU - Boor, Peter

AU - Rahimi, Khosrow

AU - Inforzato, Antonio

AU - Garlanda, Cecilia

AU - Mantovani, Alberto

AU - Anders, Hans Joachim

PY - 2018/9/25

Y1 - 2018/9/25

N2 - The long pentraxin 3 (PTX3) exerts a variety of regulatory functions in acute and chronic tissue inflammation. In particular, PTX3 acts as an opsonin for a variety of pathogens and endogenous particles. We hypothesized that PTX3 would exhibit opsonin-like functions toward calcium oxalate crystals, too, and inhibit crystal growth. This process is fundamental in kidney stone disease as well as in hyperoxaluria-related nephrocalcinosis, the paradigmatic cause of chronic kidney disease (CKD) in children with primary hyperoxaluria type I due to genetic defects in oxalate metabolism. Direct effects of PTX3 on calcium oxalate crystals were investigated in chemico by adding recombinant PTX3 to supersaturated calcium and oxalate solutions. PTX3, but not isomolar concentrations of albumin, dose-dependently inhibited crystal growth. In vivo, the PTX3 protein was undetectable in tubular epithelial cells and urine of wild-type mice under physiological conditions. However, its levels increased within 3 weeks of feeding an oxalate-rich diet, an exposure inducing hyperoxaluria-related nephrocalcinosis and CKD in selected mouse strains (male and female C57BL/6N and male Balb/c mice) but not in others (male and female 129SV and CD-1, male and female Balb/c mice). Genetic ablation of ptx3 in nephrocalcinosis un-susceptible B6;129 mice was sufficient to raise the oxalate nephropathy phenotype observed in susceptible strains. We conclude that PTX3 is an endogenous inhibitor of calcium oxalate crystal growth. This mechanism limits hyperoxaluria-related nephrocalcinosis, e.g., in primary or secondary hyperoxaluria, and potentially also in the more prevalent kidney stone disease.

AB - The long pentraxin 3 (PTX3) exerts a variety of regulatory functions in acute and chronic tissue inflammation. In particular, PTX3 acts as an opsonin for a variety of pathogens and endogenous particles. We hypothesized that PTX3 would exhibit opsonin-like functions toward calcium oxalate crystals, too, and inhibit crystal growth. This process is fundamental in kidney stone disease as well as in hyperoxaluria-related nephrocalcinosis, the paradigmatic cause of chronic kidney disease (CKD) in children with primary hyperoxaluria type I due to genetic defects in oxalate metabolism. Direct effects of PTX3 on calcium oxalate crystals were investigated in chemico by adding recombinant PTX3 to supersaturated calcium and oxalate solutions. PTX3, but not isomolar concentrations of albumin, dose-dependently inhibited crystal growth. In vivo, the PTX3 protein was undetectable in tubular epithelial cells and urine of wild-type mice under physiological conditions. However, its levels increased within 3 weeks of feeding an oxalate-rich diet, an exposure inducing hyperoxaluria-related nephrocalcinosis and CKD in selected mouse strains (male and female C57BL/6N and male Balb/c mice) but not in others (male and female 129SV and CD-1, male and female Balb/c mice). Genetic ablation of ptx3 in nephrocalcinosis un-susceptible B6;129 mice was sufficient to raise the oxalate nephropathy phenotype observed in susceptible strains. We conclude that PTX3 is an endogenous inhibitor of calcium oxalate crystal growth. This mechanism limits hyperoxaluria-related nephrocalcinosis, e.g., in primary or secondary hyperoxaluria, and potentially also in the more prevalent kidney stone disease.

KW - Colic

KW - Crystals

KW - Hyperoxaluria

KW - Kidney stone

KW - Nephrolithiasis

KW - PTX3

KW - Urolithiasis

UR - http://www.scopus.com/inward/record.url?scp=85054896717&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054896717&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2018.02173

DO - 10.3389/fimmu.2018.02173

M3 - Article

VL - 9

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

IS - SEP

M1 - 2173

ER -