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Pulmonary dysfunction and impaired granulocyte homeostasis result in poor survival of Jam-C-deficient mice

B A Imhof1, C Zimmerli, G Gliki

  • 1Department of Pathology and Immunology, Centre Médical Universitaire, 1 Rue Michel Servet, 1204, Geneva, Switzerland.

The Journal of Pathology
|April 25, 2007
PubMed

Insights

Mice lacking JAM-C (Junctional Adhesion Molecule-C) show severe pneumonia and poor survival. Restoring JAM-C in blood vessels, not other cells, significantly improves survival, highlighting its critical role in fighting infections.

Area of Science:

  • Immunology
  • Cell Biology
  • Genetics

Background:

  • Junctional Adhesion Molecule-C (JAM-C) is a protein with known roles in endothelial cells and immune cell trafficking.
  • The specific in vivo functions of JAM-C, particularly in the context of host defense and survival, remain incompletely understood.

Purpose of the Study:

  • To investigate the physiological roles of JAM-C in mice, focusing on its contribution to survival and immune responses.
  • To determine whether endothelial JAM-C expression is essential for maintaining homeostasis and preventing mortality.

Main Methods:

  • Generation and analysis of JAM-C deficient (Jam-C(-/-)) mice.
  • Phenotypic characterization including survival rates, lung pathology, and airway responsiveness.
  • Conditional rescue of JAM-C expression in endothelial cells of Jam-C(-/-) mice.

Main Results:

  • Jam-C(-/-) mice exhibited growth retardation, severe multilobular pneumonia, mega-oesophagus, and increased circulating granulocytes.
  • Endothelial cell-specific rescue of JAM-C expression restored granulocyte homeostasis.
  • Importantly, rescue of vascular JAM-C expression significantly improved survival rates in deficient mice, particularly against opportunistic infections.

Conclusions:

  • Endothelial JAM-C plays a critical role in regulating granulocyte circulation and is essential for host survival during opportunistic infections.
  • Targeting endothelial JAM-C may represent a therapeutic strategy for managing severe pneumonia and related complications.

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