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CCSP regulates cross talk between secretory cells and both ciliated cells and macrophages of the conducting airway
- Source :
- American journal of physiology. Lung cellular and molecular physiology. 293(1)
- Publication Year :
- 2007
-
Abstract
- Pulmonary host defense employs a combination of biochemical and biophysical activities to recognize, inactivate, and mediate clearance of environmental agents as well as modulate the overall response to such challenge. Dysregulation of the inflammatory arm of this response is associated with chronic lung diseases (CLD) including cystic fibrosis and chronic obstructive lung disease. Although mechanisms mediating immunoregulation are incompletely characterized, decrements in levels of the nonciliated secretory cell product Clara cell secretory protein (CCSP) in numerous CLD and identification of proinflammatory state in mice homozygous for a null allele of the CCSP gene (CCSP−/−) suggest a central role for the nonciliated secretory cell in this process. In an effort to determine the molecular basis for immunoregulatory defects associated with CCSP deficiency, we utilized difference gel electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight to compare the proteomes of wild-type and CCSP−/− mice. We demonstrate a shift in the isoelectric point of the immunomodulatory protein annexin A1 (ANXA1) to more acidic isoforms in CCSP−/− mice. Similar ANXA1 mRNA and protein abundance in wild-type and CCSP−/− tissue and identical localization of ANXA1 protein to alveolar macrophages and the ciliary bed of ciliated cells demonstrated that CCSP deficiency was associated exclusively with altered posttranslational modification of ANXA1. These results suggest that both long- and short-range paracrine signaling between nonciliated secretory cells and cells of the immune system and epithelium impact modification of cell type-specific proteins and implicate nonciliated secretory cells in a regulatory axis that might integrate critical aspects of host defense.
- Subjects :
- Pulmonary and Respiratory Medicine
Physiology
Molecular Sequence Data
Epithelium
Mice
Physiology (medical)
Cell polarity
medicine
Macrophage
Animals
Protein Isoforms
Uteroglobin
Electrophoresis, Gel, Two-Dimensional
Amino Acid Sequence
RNA, Messenger
Lung
Annexin A1
Regulation of gene expression
biology
Macrophages
Cell Polarity
Cell Biology
respiratory system
Transport protein
Mice, Inbred C57BL
Protein Transport
medicine.anatomical_structure
Gene Expression Regulation
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Immunology
biology.protein
Protein Processing, Post-Translational
Subjects
Details
- ISSN :
- 10400605
- Volume :
- 293
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- American journal of physiology. Lung cellular and molecular physiology
- Accession number :
- edsair.doi.dedup.....f1a240f77af649f49eafc8d76379d7fb