title: Defective up-regulation of CD49d in final maturation of NOD mouse macrophages.
abstract: Macrophages are potent regulators of both innate and adaptive immunity. They play a central role in the development of autoimmune diabetes and are among the first cells to appear in peri-islet infiltrates of NOD mice that spontaneously develop diabetes. Since efficient adhesion and migration are crucial for proper macrophage trafficking, we examined the migration and fibronectin (FN) adhesion capacity of NOD macrophages, as well as the regulation and expression of the FN receptors alpha4beta1 and alpha5beta1. When compared to macrophages from control strains, resident NOD macrophages showed a reduced ability to adhere to and migrate on FN, a delayed clearance following peritoneal inflammation, and substantially lower expression levels of the alpha4beta1 integrin alpha chain, CD49d. NOD bone marrow-derived macrophages were specifically defective in the LPS-induced increase in CD49d expression. Moreover, the mitogen-activated protein kinase extracellular signal-regulated kinase-1/2 negatively regulated macrophage CD49d expression and strongly suppressed its expression in NOD macrophages. The data presented herein indicate that the LPS-activated signaling cascade plays a critical role in CD49d expression of macrophages. Mature NOD macrophages are characterized by decreased CD49d expression and show defective CD49d-mediated adhesion to FN.
authors.affiliation: CNRS UMR-8147, Necker Hospital, Paris, France. s.geutskens@erasmusmc.nl
authors.forename: Sacha Brigitte
authors.initials: SB
authors.lastname: Geutskens
authors.forename: Tatjana
authors.initials: T
authors.lastname: Nikolic
authors.forename: Mireille
authors.initials: M
authors.lastname: Dardenne
authors.forename: Pieter Johannes Maria
authors.initials: PJ
authors.lastname: Leenen
authors.forename: Wilson
authors.initials: W
authors.lastname: Savino
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D039441:Integrin alpha4 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D015854:Up-Regulation / Q000502:physiology
chemical_list: D005353:Fibronectins; D008070:Lipopolysaccharides; D039441:Integrin alpha4; D048049:Extracellular Signal-Regulated MAP Kinases