Lipopolysaccharide Directly Inhibits Bicarbonate Absorption by the Renal Outer Medullary Collecting Duct

Overview

Journal Sci Rep

Specialty Science

Date 2020 Nov 26

PMID 33239624

Citations 1

Authors

Shuichi Tsuruoka

Jeffrey M Purkerson

George J Schwartz

Affiliations

Soon will be listed here.

Abstract

Acidosis is associated with E. coli induced pyelonephritis but whether bacterial cell wall constituents inhibit HCO transport in the outer medullary collecting duct from the inner stripe (OMCDi) is not known. We examined the effect of lipopolysaccharide (LPS), on HCO absorption in isolated perfused rabbit OMCDi. LPS caused a ~ 40% decrease in HCO absorption, providing a mechanism for E. coli pyelonephritis-induced acidosis. Monophosphoryl lipid A (MPLA), a detoxified TLR4 agonist, and Wortmannin, a phosphoinositide 3-kinase inhibitor, prevented the LPS-mediated decrease, demonstrating the role of TLR4-PI3-kinase signaling and providing proof-of-concept for therapeutic interventions aimed at ameliorating OMCDi dysfunction and pyelonephritis-induced acidosis.

Citing Articles

Uropathogen and host responses in pyelonephritis.

Schwartz L, Ruiz-Rosado J, Stonebrook E, Becknell B, Spencer J Nat Rev Nephrol. 2023; 19(10):658-671.

PMID: 37479904 PMC: 10913074. DOI: 10.1038/s41581-023-00737-6.

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