Junctional adhesion molecule-C regulates the early influx of leukocytes into tissues during inflammation.
Leukocyte recruitment from blood to inflammatory sites occurs in a multistep process that involves discrete molecular interactions between circulating and endothelial cells. Junctional adhesion molecule (JAM)-C is expressed at different levels on endothelial cells of lymphoid organs and peripheral tissues and has been proposed to regulate neutrophil migration by its interaction with the leukocyte integrin Mac-1. In the present study, we show that the accumulation of leukocytes in alveoli during acute pulmonary inflammation in mice is partially blocked using neutralizing Abs against JAM-C. To confirm the function of JAM-C in regulating leukocyte migration in vivo, we then generated a strain of transgenic mice overexpressing JAM-C under the control of the endothelial specific promotor Tie2. The transgenic animals accumulate more leukocytes to inflammatory sites compared with littermate control mice. Intravital microscopy shows that this is the result of increased leukocyte adhesion and transmigration, whereas rolling of leukocytes is not significantly affected in transgenic mice compared with littermates. Thus, JAM-C participates in the later steps of the leukoendothelial adhesion cascade.
Aurrand-Lions
Michel
M
Department of Pathology and Immunology, Medical University Center, Geneva, Switzerland. Michel.Aurrand-Lions@medecine.unige.ch
Lamagna
Chrystelle
C
Dangerfield
John P
JP
Wang
Shijun
S
Herrera
Pedro
P
Nourshargh
Sussan
S
Imhof
Beat A
BA
D000208:Acute Disease; D000818:Animals; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology*; D004727:Endothelium / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006098:Granulocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007136:Immunoglobulins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D008168:Lung / Q000276:immunology* / Q000473:pathology*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018715:Microscopy, Video; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology; D013997:Time Factors
D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D018836:Inflammation Mediators; C486723:Jam3 protein, mouse; D008565:Membrane Proteins