Extracellular Gelsolin Binds Lipoteichoic Acid and Modulates Cellular Response to Proinflammatory Bacterial Wall Components

The various functions of gelsolin in extracellular compartments are not yet clearly defined but include actin scavenging and anti-inflammatory 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 PIP2. The optical density 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 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 suggests 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.

BUCKI Robert;  BYFIELD Fitzroy J.;  KULAKOWSKA Alina;  MCCORMICK Margaret E.;  DROZDOWSKI Wieslaw;  NAMIOT Zbigniew;  HARTUNG Thomas;  JANMEY Paul; 

2009-07-20

AMER ASSOC IMMUNOLOGISTS

JRC45743

0022-1767,   

http://www.jimmunol.org/cgi/content/abstract/181/7/4936,    https://publications.jrc.ec.europa.eu/repository/handle/JRC45743,