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: Iris J Lee, Brendan A Hilliard, Mehriban Ulas, Daohai Yu, Chandan Vangala, Swati Rao, Jean Lee, Crystal A Gadegbeku, Philip L Cohen
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 158 Issue 2 Pg. 231-41 (Jun 2015) ISSN: 1521-7035 [Electronic] United States
• PMID: 25814173 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Intercellular Signaling Peptides and Proteins
• Protein S
• Proto-Oncogene Proteins
• growth arrest-specific protein 6
• MERTK protein, human
• Receptor Protein-Tyrosine Kinases
• c-Mer Tyrosine Kinase
• Axl Receptor Tyrosine Kinase
• AXL protein, human

Topics

• Gene Expression Regulation (physiology)
• Humans
• Inflammation
• Intercellular Signaling Peptides and Proteins (genetics, metabolism)
• Monocytes (metabolism)
• Protein S (genetics, metabolism)
• Proto-Oncogene Proteins (genetics, metabolism)
• Receptor Protein-Tyrosine Kinases (genetics, metabolism)
• Renal Insufficiency, Chronic (immunology, metabolism)
• c-Mer Tyrosine Kinase
• Axl Receptor Tyrosine Kinase