Hyaluronan fragments contribute to the ozone-primed immune response to lipopolysaccharide.

Journal Article

Hyaluronan is a high-molecular mass component of pulmonary extracelluar matrix, and lung injury can generate a low-molecular mass hyaluronan (HA) fragment that functions as endogenous ligand to cell surface receptors CD44 and TLR4. This leads to activation of intracellular NF-κB signaling and proinflammatory cytokine production. Based on previous information that ozone exposure causes increased HA in bronchial alveolar lavage fluid and ozone pre-exposure primes immune response to inhaled LPS, we hypothesized that HA production during ozone exposure augments the inflammatory response to LPS. We demonstrate that acute ozone exposure at 1 part per million for 3 h primes the immune response to low-dose aerosolized LPS in C57BL/6J mice, resulting in increased neutrophil recruitment into the airspaces, increased levels of protein and proinflammatory cytokines in the bronchoalveolar lavage fluid, and increased airway hyperresponsiveness. Intratracheal instillation of endotoxin-free HA (25 μg) enhances the biological response to inhaled LPS in a manner similar to ozone pre-exposure. In vitro studies using bone marrow-derived macrophages indicate that HA enhances LPS responses measured by TNF-α production, while immunofluorescence staining of murine alveolar macrophages demonstrates that HA induces TLR4 peripheralization and lipid raft colocalization. Collectively, our observations support that ozone primes macrophage responsiveness to low-dose LPS, in part, due to HA-induced TLR4 peripheralization in lung macrophages.

Full Text

Duke Authors

Cited Authors

  • Li, Z; Potts, EN; Piantadosi, CA; Foster, WM; Hollingsworth, JW

Published Date

  • December 1, 2010

Published In

Volume / Issue

  • 185 / 11

Start / End Page

  • 6891 - 6898

PubMed ID

  • 21037098

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1000283

Language

  • eng

Conference Location

  • United States