Impaired function of Fanconi anemia type C-deficient macrophages

Journal of Leukocyte Biology

Shehnaz Khan¹  Laura S. Haneline, –¹  Deqiang Li¹  Ying Liu¹  Kimberly Ballman¹  Ethel Derr-Yellin¹  Weinian Shou, and¹ 

[1] Departments of Pediatrics,  Microbiology and Immunology, Biochemistry and Molecular Biology, and –Cellular and Integrative Physiology, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA

关键词: inflammation;    motility;    cytoskeleton;   

DOI  :  10.1189/jlb.0811418

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

FA is a genetic disorder characterized by BM failure, developmental defects, and cancer predisposition. Previous studies suggest that FA patients exhibit alterations in immunologic function. However, it is unclear whether the defects are immune cell-autonomous or secondary to leukopenia from evolving BM failure. Given the central role that macrophages have in the innate immune response, inflammation resolution, and antigen presentation for acquired immunity, we examined whether macrophages from Fancc−/− mice exhibit impaired function. Peritoneal inflammation induced by LPS or sodium periodate resulted in reduced monocyte/macrophage recruitment in Fancc−/− mice compared with WT controls. Fancc−/− mice also had decreased inflammatory monocytes mobilized into the peripheral blood after LPS treatment compared with controls. Furthermore, Fancc−/− peritoneal macrophages displayed cell-autonomous defects in function, including impaired adhesion to FN or endothelial cells, reduced chemoattractant-mediated migration, and decreased phagocytosis. Moreover, dysregulated F-actin rearrangement was detected in Fancc−/− macrophages after adhesion to FN, which was consistent with an observed reduction in RhoA-GTP levels. Importantly, these data suggest that impaired cytoskeletal rearrangements in Fancc−/− macrophages may be the common mechanism responsible for cell-autonomous defects detected in vitro, as well as altered monocyte/macrophage trafficking in vivo.

【 授权许可】

Unknown