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Abl family kinases regulate FcγR-mediated phagocytosis in murine macrophages.

Publication ,  Journal Article
Greuber, EK; Pendergast, AM
Published in: Journal of immunology (Baltimore, Md. : 1950)
December 2012

Phagocytosis of Ab-coated pathogens is mediated through FcγRs, which activate intracellular signaling pathways to drive actin cytoskeletal rearrangements. Abl and Arg define a family of nonreceptor tyrosine kinases that regulate actin-dependent processes in a variety of cell types, including those important in the adaptive immune response. Using pharmacological inhibition as well as dominant negative and knockout approaches, we demonstrate a role for the Abl family kinases in phagocytosis by macrophages and define a mechanism whereby Abl kinases regulate this process. Bone marrow-derived macrophages from mice lacking Abl and Arg kinases exhibit inefficient phagocytosis of sheep erythrocytes and zymosan particles. Treatment with the Abl kinase inhibitors imatinib and GNF-2 or overexpression of kinase-inactive forms of the Abl family kinases also impairs particle internalization in murine macrophages, indicating Abl kinase activity is required for efficient phagocytosis. Further, Arg kinase is present at the phagocytic cup, and Abl family kinases are activated by FcγR engagement. The regulation of phagocytosis by Abl family kinases is mediated in part by the spleen tyrosine kinase (Syk). Loss of Abl and Arg expression or treatment with Abl inhibitors reduced Syk phosphorylation in response to FcγR ligation. The link between Abl family kinases and Syk may be direct, as purified Arg kinase phosphorylates Syk in vitro. Further, overexpression of membrane-targeted Syk in cells treated with Abl kinase inhibitors partially rescues the impairment in phagocytosis. Together, these findings reveal that Abl family kinases control the efficiency of phagocytosis in part through the regulation of Syk function.

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Published In

Journal of immunology (Baltimore, Md. : 1950)

DOI

EISSN

1550-6606

ISSN

0022-1767

Publication Date

December 2012

Volume

189

Issue

11

Start / End Page

5382 / 5392

Related Subject Headings

  • Syk Kinase
  • Signal Transduction
  • Sheep
  • Receptors, IgG
  • Pyrimidines
  • Proto-Oncogene Proteins c-abl
  • Protein-Tyrosine Kinases
  • Protein Kinase Inhibitors
  • Protein Binding
  • Primary Cell Culture
 

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Greuber, E. K., & Pendergast, A. M. (2012). Abl family kinases regulate FcγR-mediated phagocytosis in murine macrophages. Journal of Immunology (Baltimore, Md. : 1950), 189(11), 5382–5392. https://doi.org/10.4049/jimmunol.1200974
Greuber, Emileigh K., and Ann Marie Pendergast. “Abl family kinases regulate FcγR-mediated phagocytosis in murine macrophages.Journal of Immunology (Baltimore, Md. : 1950) 189, no. 11 (December 2012): 5382–92. https://doi.org/10.4049/jimmunol.1200974.
Greuber EK, Pendergast AM. Abl family kinases regulate FcγR-mediated phagocytosis in murine macrophages. Journal of immunology (Baltimore, Md : 1950). 2012 Dec;189(11):5382–92.
Greuber, Emileigh K., and Ann Marie Pendergast. “Abl family kinases regulate FcγR-mediated phagocytosis in murine macrophages.Journal of Immunology (Baltimore, Md. : 1950), vol. 189, no. 11, Dec. 2012, pp. 5382–92. Epmc, doi:10.4049/jimmunol.1200974.
Greuber EK, Pendergast AM. Abl family kinases regulate FcγR-mediated phagocytosis in murine macrophages. Journal of immunology (Baltimore, Md : 1950). 2012 Dec;189(11):5382–5392.

Published In

Journal of immunology (Baltimore, Md. : 1950)

DOI

EISSN

1550-6606

ISSN

0022-1767

Publication Date

December 2012

Volume

189

Issue

11

Start / End Page

5382 / 5392

Related Subject Headings

  • Syk Kinase
  • Signal Transduction
  • Sheep
  • Receptors, IgG
  • Pyrimidines
  • Proto-Oncogene Proteins c-abl
  • Protein-Tyrosine Kinases
  • Protein Kinase Inhibitors
  • Protein Binding
  • Primary Cell Culture