Abstract

Myeloid leukocytes form actin-based plasma membrane protrusions, called podosomes, that are implicated in myeloid cell recruitment into tissues and cell migration within the interstitium. In this study, we show that tyrosine kinases of the Abl family are present in podosomes formed by murine and human macrophages. Silencing of Abl expression in bone marrow-derived macrophages and monocyte-derived macrophages by siRNA or Abl enzymatic inhibition with imatinib resulted in the disassembly of macrophage podosomes and the reduction of their capacity to degrade an extracellular matrix and migrate through matrigel matrices and endothelial cell monolayers. Additionally, macrophages deficient in Src-family kinases, which cross-talk with Abl in regulating macrophage migration, also demonstrated podosome disassembly. These findings suggest that podosome disassembly induced by Abl targeting may inhibit podosome-dependent functions such as leukocyte recruitment into inflammatory sites and osteoclast-dependent bone resorption.

Links

Publisher Full Text

Authors

Baruzzi A, Berton G

Institution

Department of Pathology and Diagnostics, Section of General Pathology, University of Verona, Verona, Italy.

Source

European journal of immunology 42:10 2012 Oct pg 2720-6

MeSH

Actins
Animals
Cell Movement
Cell Surface Extensions
Cells, Cultured
Humans
Macrophages
Mice
Mice, Inbred C57BL
Oncogene Proteins v-abl
Piperazines
Protein Kinase Inhibitors
Protein-Tyrosine Kinases
Pyrimidines
RNA, Small Interfering

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22733220