Deficiency of AXL in Bone Marrow-Derived Cells Does Not Affect Advanced Atherosclerotic Lesion Progression

Sci Rep. 2016 Dec 13:6:39111. doi: 10.1038/srep39111.

Abstract

AXL, a member of the TAM (Tyro3, Axl, MerTK) family of receptors, plays important roles in cell survival, clearance of dead cells (efferocytosis), and suppression of inflammation, which are processes that critically influence atherosclerosis progression. Whereas MerTK deficiency promotes defective efferocytosis, inflammation, and plaque necrosis in advanced murine atherosclerosis, the role of Axl in advanced atherosclerosis progression is not known. Towards this end, bone marrow cells from Axl-/- or wild-type mice were transplanted into lethally irradiated Ldlr-/- mice. These chimeric mice were then fed the Western-type diet (WD) for 17 weeks. We demonstrate that lesional macrophages in WT mice express Axl but that Axl deficiency in bone marrow-derived cells does not affect lesion size, cellularity, necrosis, or inflammatory parameters in advanced atherosclerotic plaques. Moreover, apoptosis of lesional cells was unaffected, and we found no evidence of defective lesional efferocytosis. In contrast to previously reported findings with MerTK deficiency, hematopoietic cell-Axl deficiency in WD-fed Ldlr-/- mice does not affect the progression of advanced atherosclerosis or lesional processes associated with TAM receptor signaling. These findings suggest a heretofore unappreciated TAM receptor hierarchy in advanced atherosclerosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Axl Receptor Tyrosine Kinase
  • Bone Marrow Cells / metabolism*
  • Bone Marrow Transplantation
  • Disease Models, Animal
  • Disease Progression
  • Gene Knockout Techniques
  • Macrophages / immunology
  • Macrophages / pathology*
  • Mice
  • Plaque, Atherosclerotic / immunology
  • Plaque, Atherosclerotic / pathology*
  • Proto-Oncogene Proteins / deficiency*
  • Receptor Protein-Tyrosine Kinases / deficiency*
  • Receptors, LDL / genetics

Substances

  • Proto-Oncogene Proteins
  • Receptors, LDL
  • Receptor Protein-Tyrosine Kinases
  • Axl Receptor Tyrosine Kinase
  • AXL receptor tyrosine kinase, mouse