Junctional Adhesion Molecule-C Mediates Leukocyte Infiltration in Response to Ischemia Reperfusion Injury

Autor: Costantino Pitzalis, Sussan Nourshargh, Alessandra Marrelli, Michel Aurrand-Lions, Christoph Scheiermann, Christoph Thiemermann, Paolo Meda, Nimesh S. A. Patel, Beat A. Imhof, Abigail Woodfin, Bartomeu Colom, Mathieu-Benoit Voisin
Rok vydání: 2009
Předmět:
Leukocyte migration
Pathology
medicine.medical_specialty
Immunoelectron microscopy
education
Immunoglobulins
Mice
Transgenic
ddc:616.07
Endothelial Cells/metabolism
Kidney
Article
Mice
03 medical and health sciences
0302 clinical medicine
Cell Movement
Cell Adhesion
Leukocytes
medicine
Animals
ddc:612
Muscle
Skeletal
Cell adhesion
030304 developmental biology
Leukocytes/physiology
0303 health sciences
Kidney/blood supply
Cell adhesion molecule
business.industry
Cell Adhesion Molecules/analysis/physiology
fungi
Endothelial Cells
medicine.disease
humanities
Cell biology
Mice
Inbred C57BL
Reperfusion Injury
030220 oncology & carcinogenesis
Cremaster muscle
cardiovascular system
Muscle
Skeletal/blood supply
Reperfusion Injury/pathology
Cardiology and Cardiovascular Medicine
business
Cell Adhesion Molecules
Junctional Adhesion Molecule C
Reperfusion injury
Immunoglobulins/analysis/physiology
Intravital microscopy
Zdroj: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 29, No 10 (2009) pp. 1509-15
Arteriosclerosis, Thrombosis, and Vascular Biology; Vol 29
Arteriosclerosis, Thrombosis, and Vascular Biology
ISSN: 1524-4636
1079-5642
DOI: 10.1161/atvbaha.109.187559
Popis: Objective—Junctional adhesion molecule-C (JAM-C) is an adhesion molecule that has multiple roles in inflammation and vascular biology, but many aspects of its functions under pathological conditions are unknown. Here we investigated the role of JAM-C in leukocyte migration in response to ischemia reperfusion (I/R) injury.Methods and Results—Pretreatment of mice with soluble JAM-C (sJAM-C), used as a pharmacological blocker of JAM-C-mediated reactions, significantly suppressed leukocyte migration in models of kidney and cremaster muscle I/R injury (39 and 51% inhibition, respectively). Furthermore, in the cremaster muscle model (studied by intravital microscopy), both leukocyte adhesion and transmigration were suppressed in JAM-C-deficient mice (JAM-C−/−) and enhanced in mice overexpressing JAM-C in their endothelial cells (ECs). Analysis of JAM-C subcellular expression by immunoelectron microscopy indicated that in I/R-injured tissues, EC JAM-C was redistributed from cytoplasmic vesicles and EC junctional sites to nonjunctional plasma membranes, a response that may account for the role of JAM-C in both leukocyte adhesion and transmigration under conditions of I/R injury.Conclusions—The findings demonstrate a role for EC JAM-C in mediating leukocyte adhesion and transmigration in response to I/R injury and indicate the existence of a novel regulatory mechanism for redistribution and hence function of EC JAM-C in vivo.
Databáze: OpenAIRE
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