Pulmonary dysfunction and impaired granulocyte homeostasis result in poor survival of Jam-C-deficient mice.
Jam-C(-/-) mice exhibit growth retardation and multilobular pneumonia concomitant with poor survival of the mice under conventional housing conditions. The deficient mice present a mega-oesophagus and have altered airway responsiveness. In addition, the number of circulating granulocytes is increased in Jam-C(-/-) mice as compared to control animals. These phenotypes probably reflect the different functions of JAM-C expressed by endothelial and mesenchymal cells. Indeed, the deregulation in the number of circulating granulocytes is caused by the lack of JAM-C expression on endothelial cells since rescuing endothelial expression of the protein in the Jam-C(-/-) mice is sufficient to restore homeostasis. More importantly, the rescue of vascular JAM-C expression is accompanied by better survival of deficient mice, suggesting that endothelial expression of JAM-C is mandatory for animal survival from opportunistic infections and fatal pneumonia.
Imhof
B A
BA
Department of Pathology and Immunology, Centre Médical Universitaire, 1 Rue Michel Servet, 1204, Geneva, Switzerland.
Zimmerli
C
C
Gliki
G
G
Ducrest-Gay
D
D
Juillard
P
P
Hammel
P
P
Adams
R
R
Aurrand-Lions
M
M
D000818:Animals; D001980:Bronchi / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000172:deficiency* / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology; D004931:Esophageal Achalasia / Q000276:immunology / Q000503:physiopathology; D004947:Esophagus / Q000276:immunology / Q000503:physiopathology; D006098:Granulocytes / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology*; D007136:Immunoglobulins / Q000032:analysis / Q000172:deficiency* / Q000276:immunology; D007150:Immunohistochemistry / Q000379:methods; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology* / Q000503:physiopathology; D008565:Membrane Proteins / Q000032:analysis / Q000172:deficiency* / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D009130:Muscle, Smooth / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010538:Peritonitis / Q000276:immunology / Q000503:physiopathology; D011014:Pneumonia / Q000276:immunology; D019718:Receptors, CXCR4 / Q000032:analysis
C514936:CXCR4 protein, mouse; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C486723:Jam3 protein, mouse; D008565:Membrane Proteins; D019718:Receptors, CXCR4