The tyrosine kinase Abl is a component of macrophage podosomes and is required for podosome formation and function.
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.
Department of Pathology and Diagnostics, Section of General Pathology, University of Verona, Verona, Italy.
SourceEuropean journal of immunology 42:10 2012 Oct pg 2720-6
Cell Surface Extensions
Mice, Inbred C57BL
Oncogene Proteins v-abl
Protein Kinase Inhibitors
RNA, Small Interfering
Pub Type(s)Journal Article
Research Support, Non-U.S. Gov't