title: Monocyte and plasma expression of TAM ligand and receptor in renal failure: Links to unregulated immunity and chronic inflammation.
abstract: Chronic inflammation is increased in patients with chronic kidney disease (CKD) and contributes to cardiovascular morbidity and mortality. Specific immune mechanisms and pathways that drive and maintain chronic inflammation in CKD are not well described. The TAM ligands (Gas6 and protein S) and receptors (Axl and Mer) have been recently recognized as playing a prominent role in immune regulation. The receptors exist in both soluble and cell-bound forms; the soluble receptors (sAxl and sMer) are believed to compete with the bound receptors and thus inhibit their function. In this study, we determined the expression of cell-bound and soluble TAM proteins in patients with CKD. CKD patients had significantly lower expression of Mer in monocytes, yet increased expression of soluble TAM receptors sAxl and sMer in plasma compared to controls. The metalloproteinase ADAM 17, responsible for cleavage of Mer to its soluble form, was increased in patient monocytes. Elevated levels of soluble TAM receptors were more evident in patients with progressive renal failure. These observations suggest that functional deficiency of TAM receptor-mediated regulation of inflammation may contribute to chronic inflammation in patients with CKD.
authors: Section of Nephrology, Department of Medicine, Temple University, Philadelphia, PA, USA. Electronic address: iris.lee@tuhs.temple.edu.
authors: Iris J
authors: IJ
authors: Lee
authors: Section of Rheumatology, Department of Medicine, Temple University, Philadelphia, PA, USA.
authors: Brendan A
authors: BA
authors: Hilliard
authors: Section of Rheumatology, Department of Medicine, Temple University, Philadelphia, PA, USA.
authors: Mehriban
authors: M
authors: Ulas
authors: Department of Clinical Sciences, Temple University, Philadelphia, PA, USA.
authors: Daohai
authors: D
authors: Yu
authors: School of Medicine, Temple University, Philadelphia, PA, USA.
authors: Chandan
authors: C
authors: Vangala
authors: Section of Nephrology, Department of Medicine, Temple University, Philadelphia, PA, USA.
authors: Swati
authors: S
authors: Rao
authors: Section of Nephrology, Department of Medicine, Temple University, Philadelphia, PA, USA.
authors: Jean
authors: J
authors: Lee
authors: Section of Nephrology, Department of Medicine, Temple University, Philadelphia, PA, USA.
authors: Crystal A
authors: CA
authors: Gadegbeku
authors: Section of Rheumatology, Department of Medicine, Temple University, Philadelphia, PA, USA.
authors: Philip L
authors: PL
authors: Cohen
mesh_terms: D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007249:Inflammation; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D017293:Protein S / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D051436:Renal Insufficiency, Chronic / Q000276:immunology / Q000378:metabolism*; D000076202:c-Mer Tyrosine Kinase; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D017293:Protein S; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6; C097072:MERTK protein, human; C000722289:AXL protein, human
keywords: Axl; Chronic kidney disease; Inflammation; Mer; Monocytes; TAM receptors