Extracellular gelsolin binds lipoteichoic acid and modulates cellular response to proinflammatory bacterial wall components

Robert Bucki, Fitzroy J. Byfield, Alina Kulakowska, Margaret E. McCormick, Wieslaw Drozdowski, Zbigniew Namiot, Thomas Hartung, Paul A. Janmey

Research output: Contribution to journalArticlepeer-review

Abstract

The various functions of gelsolin in extracellular compartments are not yet clearly defined but include actin scavenging and antiin-flammatory effects. Gelsolin was recently reported to bind endotoxin (LPS) from various Gram-negative bacteria with high affinity. In this study we investigate whether gelsolin also interacts with bacterial wall molecules of Gram-positive bacteria such as lipoteichoic acid (LTA) and whether gelsolin's interaction with bacterial lipids from Gram-negative or Gram-positive bacteria affects their cellular inflammatory responses. A peptide based on the PPI binding site of gelsolin (160 -169) binds purified LTA at the same molecular ratio that it binds phosphatidylinositol 4,5-bisphosphate. The OD of recombinant human plasma gelsolin was found to decrease following the addition of purified LTA, and the binding of gelsolin to LTA inhibits F-actin depolymerization by gelsolin. Simultaneously, the ability of LTA to activate translocation of NF-κB, E-selectin expression, and adhesion of neutrophils to LTA-treated human aortic endothelial cells was compromised by gelsolin. Gelsolin was able to partially inhibit LPS- or LTA-induced release of IL-8 from human neutrophils but was unable to prevent Gram-positive Bacillus subtilis or Gram-negative Pseudomonas aeruginosa growth and had no effect on the antibacterial activity of the cathelicidin-derived antibacterial peptide LL37. These data suggest that extracellular gelsolin is involved in the host immune recognition of LTA or LPS following release of these molecules from the bacterial outer membrane during cell division or attack by drugs and immune components.

Original languageEnglish (US)
Pages (from-to)4936-4944
Number of pages9
JournalJournal of Immunology
Volume181
Issue number7
DOIs
StatePublished - Oct 1 2008
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'Extracellular gelsolin binds lipoteichoic acid and modulates cellular response to proinflammatory bacterial wall components'. Together they form a unique fingerprint.

Cite this