Impaired function of Fanconi anemia type C-deficient macrophages

Ying Liu, Kimberly Ballman, Deqiang Li, Shehnaz Khan, Ethel Derr-Yellin, Weinian Shou, Laura Haneline

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)333-340
Number of pages8
JournalJournal of Leukocyte Biology
Volume91
Issue number2
DOIs
StatePublished - Feb 2012

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Fanconi Anemia
Macrophages
Monocytes
Inflammation
Inborn Genetic Diseases
Chemotactic Factors
Leukopenia
Antigen Presentation
Peritoneal Macrophages
Adaptive Immunity
Guanosine Triphosphate
Phagocytosis
Innate Immunity
Actins
Endothelial Cells
Neoplasms

Keywords

  • Cytoskeleton
  • Inflammation
  • Motility

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

Impaired function of Fanconi anemia type C-deficient macrophages. / Liu, Ying; Ballman, Kimberly; Li, Deqiang; Khan, Shehnaz; Derr-Yellin, Ethel; Shou, Weinian; Haneline, Laura.

In: Journal of Leukocyte Biology, Vol. 91, No. 2, 02.2012, p. 333-340.

Research output: Contribution to journalArticle

Liu, Ying ; Ballman, Kimberly ; Li, Deqiang ; Khan, Shehnaz ; Derr-Yellin, Ethel ; Shou, Weinian ; Haneline, Laura. / Impaired function of Fanconi anemia type C-deficient macrophages. In: Journal of Leukocyte Biology. 2012 ; Vol. 91, No. 2. pp. 333-340.
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