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Defective up‐regulation of CD49d in final maturation of NOD mouse macrophages
Author(s) -
Geutskens Sacha Brigitte,
Nikolic Tatjana,
Dardenne Mireille,
Leenen Pieter Johannes Maria,
Savino Wilson
Publication year - 2004
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200425259
Subject(s) - nod , microbiology and biotechnology , biology , macrophage , nod mice , fibronectin , innate immune system , inflammation , immunology , immune system , extracellular matrix , endocrinology , in vitro , biochemistry , diabetes mellitus
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 α4β1 and α5β1. 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 α4β1 integrin α 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.