title: Lutheran/basal cell adhesion molecule accelerates progression of crescentic glomerulonephritis in mice.
abstract: Migration of circulating leukocytes from the vasculature into the surrounding tissue is an important component of the inflammatory response. Among the cell surface molecules identified as contributing to leukocyte extravasation is VCAM-1, expressed on activated vascular endothelium, which participates in all stages of leukocyte-endothelial interaction by binding to leukocyte surface expressed integrin VLA-4. However, not all VLA-4-mediated events can be linked to VCAM-1. A novel interaction between VLA-4 and endothelial Lutheran (Lu) blood group antigens and basal cell adhesion molecule (BCAM) proteins has been recently shown, suggesting that Lu/BCAM may have a role in leukocyte recruitments in inflamed tissues. Here, we assessed the participation of Lu/BCAM in the immunopathogenesis of crescentic glomerulonephritis. High expression of Lu/BCAM in glomeruli of mice with rapidly progressive glomerulonephritis suggests a potential role for the local expression of Lu/BCAM in nephritogenic recruitment of leukocytes. Genetic deficiency of Lu/BCAM attenuated glomerular accumulation of T cells and macrophages, crescent formation, and proteinuria, correlating with reduced fibrin and platelet deposition in glomeruli. Furthermore, we found a pro-adhesive interaction between human monocyte α4β1 integrin and Lu/BCAM proteins. Thus, Lu/BCAM may have a critical role in facilitating the accumulation of monocytes and macrophages, thereby exacerbating renal injury.
authors.affiliation: 1] Paris Cardiovascular Research Centre, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France [2] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.affiliation: 1] Université Paris Diderot, Sorbonne Paris Cité, Paris, France [2] Unité Mixte de Recherche 995, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France [3] Institut National de la Transfusion Sanguine (INTS), Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Filipe
authors.affiliation: 1] Université Paris Diderot, Sorbonne Paris Cité, Paris, France [2] Unité Mixte de Recherche 995, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France [3] Institut National de la Transfusion Sanguine (INTS), Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Rahuel
authors.affiliation: 1] Université Paris Diderot, Sorbonne Paris Cité, Paris, France [2] Service d'Exploration Fonctionnelles, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France [3] Institut National de la Santé et de la Recherche Médicale (INSERM) U965, Hôpital Lariboisière, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bonnin
authors.affiliation: 1] Unité Mixte de Recherche 702, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France [2] Université Pierre et Marie Curie, Sorbonne Universités, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Mesnard
authors.affiliation: 1] Paris Cardiovascular Research Centre, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France [2] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Guérin
authors.affiliation: 1] Paris Cardiovascular Research Centre, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France [2] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1] Université Paris Diderot, Sorbonne Paris Cité, Paris, France [2] Unité Mixte de Recherche 995, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France [3] Institut National de la Transfusion Sanguine (INTS), Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Le Van Kim
authors.affiliation: 1] Université Paris Diderot, Sorbonne Paris Cité, Paris, France [2] Unité Mixte de Recherche 995, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France [3] Institut National de la Transfusion Sanguine (INTS), Paris, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Colin
authors.affiliation: 1] Paris Cardiovascular Research Centre, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France [2] Université Paris Descartes, Sorbonne Paris Cité, Paris, France [3] Service de Néphrologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Pierre-Louis
authors.initials: PL
authors.lastname: Tharaux
mesh_terms: D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D001323:Autoantibodies; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D002634:Chemotaxis, Leukocyte; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism; D007668:Kidney / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D008188:Lutheran Blood-Group System; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D051437:Renal Insufficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D001323:Autoantibodies; C477645:Bcam protein, mouse; D015815:Cell Adhesion Molecules; D039041:Integrin alpha4beta1; D008188:Lutheran Blood-Group System; D008562:Membrane Glycoproteins; C051951:antiglomerular basement membrane antibody