title: Deficiency of AXL in Bone Marrow-Derived Cells Does Not Affect Advanced Atherosclerotic Lesion Progression.
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.
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, USA.|CSIR - Institute of Genomics and Integrative Biology, New Delhi, India.
authors.forename: Manikandan
authors.initials: M
authors.lastname: Subramanian
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Proto
authors.affiliation: Department of Microbiology &Immunology, UNC Neuroscience Center, Integrative Program in Biological Genome Sciences, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Glenn K
authors.initials: GK
authors.lastname: Matsushima
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, USA.|Department of Pathology and Cell Biology, Columbia University Medical Center, New York, USA.|Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, USA.
authors.forename: Ira
authors.initials: I
authors.lastname: Tabas
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D004195:Disease Models, Animal; D018450:Disease Progression; D055786:Gene Knockout Techniques; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D051379:Mice; D058226:Plaque, Atherosclerotic / Q000276:immunology / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000172:deficiency*; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency*; D011973:Receptors, LDL / Q000235:genetics; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D011518:Proto-Oncogene Proteins; D011973:Receptors, LDL; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; C000722290:AXL receptor tyrosine kinase, mouse