Advanced glycation end products enhance monocyte activation during human mixed lymphocyte reaction

• Published in: Clinical immunology (Orlando, Fla.) Vol. 134; no. 3; pp. 345 - 353
• Main Authors: Ohashi, Katsuhisa, Takahashi, Hideo Kohka, Mori, Shuji, Liu, Keyue, Wake, Hidenori, Sadamori, Hiroshi, Matsuda, Hiroaki, Yagi, Takahito, Yoshino, Tadashi, Nishibori, Masahiro, Tanaka, Noriaki
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.03.2010; Elsevier
• Subjects: Advanced glycation end products; Allergy and Immunology; Biological and medical sciences; Cell Adhesion Molecules - immunology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glycation End Products, Advanced - immunology; Humans; Kinetics; Lymphocyte Activation - immunology; Lymphocyte Culture Test, Mixed - methods; Medical sciences; Mixed lymphocyte reaction; Monocytes - immunology; Posttransplant diabetes mellitus; Receptor for Advanced Glycation End Products; Receptors, Immunologic - immunology; Advanced glycation end products; Mixed lymphocyte reaction; Posttransplant diabetes mellitus; Endocrinopathy; Human; Monocyte; Diabetes mellitus; Activation; Transplantation; Immunology; Treatment; Surgery; Graft
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2009.10.008

Abstract Posttransplant diabetes mellitus (PTDM) is a frequent complication among transplant recipients. Ligation of advanced glycation end products (AGEs) with their receptor (RAGE) on monocytes/macrophages plays roles in the diabetes complications. The enhancement of adhesion molecule expression on monocytes/macrophages activates T-cells, leading to reduced allograft survival. We investigated the effect of four distinct AGE subtypes (AGE-2/AGE-3/AGE-4/AGE-5) on the expressions of intracellular adhesion molecule (ICAM)-1, B7.1, B7.2 and CD40 on monocytes, the production of interferon (IFN)-γ and tumor necrosis factor (TNF)-α and the proliferation of T-cells during human mixed lymphocyte reaction (MLR). AGE-2 and AGE-3 selectively induced the adhesion molecule expression, cytokine production and T-cell proliferation. The AGE-induced up-regulation of adhesion molecule expression was involved in the cytokine production and T-cell proliferation. AGE-2 and AGE-3 up-regulated the expression of RAGE on monocytes; therefore, the AGEs may activate monocytes, leading to the up-regulation of adhesion molecule expression, cytokine production and T-cell proliferation.