Histamine inhibits adhesion molecule expression in human monocytes, induced by advanced glycation end products, during the mixed lymphocyte reaction

J. Zhang, H. K. Takahashi, K. Liu, H. Wake, R. Liu, H. Sadamori, H. Matsuda, T. Yagi, T. Yoshino, S. Mori, M. Nishibori

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background and purpose: Post-transplant diabetes mellitus is a frequent complication among transplant recipients. Ligation of advanced glycation end products (AGEs) with their receptor on monocytes/macrophages plays important roles in the genesis of diabetic complications. The enhancement of adhesion molecule expression on monocytes/macrophages activates T-cells, reducing allograft survival. Out of four distinct AGE subtypes (AGE-2, AGE-3, AGE-4 and AGE-5), only AGE-2 and AGE-3 induced expression of intercellular adhesion molecules (ICAMs), output of cytokines and proliferation of lymphocytes, during the mixed lymphocyte reaction (MLR). Here we have assessed the role of histamine in the actions of AGEs during the MLR. Experimental approach: Human peripheral blood cells were used in these experiments. Flow cytometry was used to examine the expression of the ICAM-1, B7.1, B7.2 and CD40. Production of the cytokine interferon-γ, and levels of cAMP were determined by elisa. Lymphocyte proliferation was determined by [3H]-thymidine uptake. Key results: Histamine concentration dependently inhibited the action of AGE-2 and AGE-3. The actions of histamine were antagonized by an H2-receptor antagonist, famotidine, and mimicked by H2/H4-receptor agonists, dimaprit and 4-methylhistamine. The effects of histamine were reversed by a protein kinase A (PKA) inhibitor, H89, and mimicked by dibutyryl cAMP and an adenylate cyclase activator, forskolin. Conclusions and implications: Histamine down-regulated AGE-2- and AGE-3-induced expression of adhesion molecules, cytokine production and lymphocyte proliferation via histamine H2 receptors and the cAMP/PKA pathway.

Original languageEnglish
Pages (from-to)1378-1386
Number of pages9
JournalBritish Journal of Pharmacology
Volume160
Issue number6
DOIs
Publication statusPublished - Jul 2010

Keywords

  • adhesion molecule
  • advanced glycation end products
  • cyclic adenosine monophosphate
  • diabetes
  • histamine
  • human mixed lymphocyte reaction
  • monocytes
  • transplantation

ASJC Scopus subject areas

  • Pharmacology

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