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PMID: 11786905 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Platelet-activating factor receptor and ADAM10 mediate responses to Staphylococcus aureus in epithelial cells.

Nature medicine ·Vol. 8 ·No. 1 ·2002-01-00 ·Pages 41-6

Lemjabbar H, Basbaum C

Abstract

In the lungs of cystic fibrosis patients, overproduction of mucus leads to morbidity and mortality by obstructing airflow and shielding bacteria from antibiotics. Here we demonstrate that overproduction of mucus is a direct result of the activation of mucin gene expression by Gram-positive bacteria. Bacterial lipoteichoic acid activates the platelet-activating factor receptor, which is G protein-coupled. This results in activation of a disintegrin and metalloproteinase (ADAM10), kuzbanian, cleavage of pro heparin-binding epidermal growth factor and activation of the epidermal growth factor receptor. Unlike responses in macrophages, the epithelial-cell response to lipoteichoic acid does not require Toll-like receptor 2 or 4.

MeSH Terms

Amyloid Precursor Protein Secretases Aspartic Acid Endopeptidases Disintegrins/metabolism Drosophila Proteins Endopeptidases/metabolism Epithelial Cells/microbiology ErbB Receptors/genetics Gram-Positive Bacteria/pathogenicity Humans Lipopolysaccharides/pharmacology Lung/pathology Membrane Glycoproteins/metabolism Metalloendopeptidases/metabolism Models, Genetic Mucin-2 Mucins/biosynthesis Mucus/metabolism Platelet Membrane Glycoproteins/metabolism Receptors, Cell Surface/metabolism Receptors, G-Protein-Coupled Signal Transduction Staphylococcal Infections/pathology Staphylococcus aureus/pathogenicity Teichoic Acids/pharmacology Toll-Like Receptor 2 Toll-Like Receptors Transcriptional Activation

Chemicals

Disintegrins Drosophila Proteins Lipopolysaccharides MUC2 protein, human Membrane Glycoproteins Mucin-2 Mucins Platelet Membrane Glycoproteins Receptors, Cell Surface Receptors, G-Protein-Coupled TLR2 protein, human Teichoic Acids Toll-Like Receptor 2 Toll-Like Receptors platelet activating factor receptor lipoteichoic acid ErbB Receptors Amyloid Precursor Protein Secretases Endopeptidases Aspartic Acid Endopeptidases BACE1 protein, human KUZ protein, Drosophila Metalloendopeptidases

Authors & Affiliations

2 authors, click to expand affiliations / ORCID

Lemjabbar Hassan

Biomedical Sciences Program, Cardiovascular Research Institute and Department of Anatomy, University of California, San Francisco, California, USA.

Basbaum Carol

Article Info

Journal

Nature medicine

Abbr.

Nat Med

ISSN

1078-8956

DOI

10.1038/nm0102-41

Published

2002-01-00

Pages

41-6

Language

English

Region

United States

NLM ID

9502015

Subset

Grants

NHLBI NIH HHS · HL24136 · United States

NHLBI NIH HHS · HL43726 · United States

External Links

PubMed source DOI: 10.1038/nm0102-41 View journal details

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Platelet-activating factor receptor and ADAM10 mediate responses to Staphylococcus aureus in epithelial cells.

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