Advanced glycosylation endproduct-specific receptors on human and rat t-lymphocytes mediate synthesis of interferon γ

Role in tissue remodeling

Farhad Imani, Yasuhiro Horii, Manikkam Suthanthiran, Edward Y. Skolnik, Zenji Makita, Vijay Sharma, Prabodh Sehajpal, Helen Vlassara

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

During normal aging and in chronic diabetes the excessive accumulation of reactive glucoseprotein or glucose-lipid adducts known as advanced glycosylation endproducts (AGES) has been shown to induce tissue dysfunction, in part through interaction with AGE-specific receptors on monocyte/macrophages and other cells. Recognizing that circulating lymphocytes trafficking through tissues interact with tissue AGES, we searched for the expression of AGE-binding sites on peripheral blood T lymphocytes. Resting rat and human T cells bound 125I-AGE-albumin with an affinity of 7.8 × 101 M−1, whereas, after stimulation with phytohemagglutinin (PHA) for 48 h, binding affinity increased to 5.8 × 108 M−1. Flow cytometric analysis of resting rat T cells using polyclonal antibodies raised against rat liver AGE-binding proteins (p60 and p90) revealed the constitutive expression of both immunoreactivities. The number of resting CD4+ and CD8+ T cells positive for anti-p60 antibody binding (34.2 and 58.5%, respectively) increased to 92 and 90% of cells after 48-h stimulation with PHA. Exposure of PHA-activated T lymphocytes to AGE-albumin enhanced expression of interferon γ (IFN-γ) mRNA 10-fold and induced greater elaboration of the mature protein than did exposure to unmodified protein or PHA treatment alone. These data indicate that T cells contain an inducible system of surface receptors for AGE-modified proteins, and that receptor occupancy is linked to lymphokine production. This T cell AGE-receptor system might serve to target lymphocytes to AGE-rich tissues and involve them in the regulation of tissue homeostasis either by assisting in macrophagedependent clearance of AGE-proteins, or by exerting direct antiproliferative action on mesenchymal cells. Under conditions of excessive AGE-protein and AGE lipid accumulation (e.g., aging and diabetes), enhanced production of AGE-induced IFN-γ may accelerate immune responses that contribute to tissue injury.

Original languageEnglish
Pages (from-to)2165-2172
Number of pages8
JournalJournal of Experimental Medicine
Volume178
Issue number6
DOIs
Publication statusPublished - 1 Dec 1993
Externally publishedYes

Fingerprint

Glycosylation
Interferons
Phytohemagglutinins
Lymphocytes
T-Lymphocytes
Proteins
Albumins
Lipids
Lymphokines
T-Cell Antigen Receptor
Monocytes
Anti-Idiotypic Antibodies
Carrier Proteins
Homeostasis
Macrophages
Binding Sites
Glucose
Messenger RNA
Antibodies
Liver

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Advanced glycosylation endproduct-specific receptors on human and rat t-lymphocytes mediate synthesis of interferon γ : Role in tissue remodeling. / Imani, Farhad; Horii, Yasuhiro; Suthanthiran, Manikkam; Skolnik, Edward Y.; Makita, Zenji; Sharma, Vijay; Sehajpal, Prabodh; Vlassara, Helen.

In: Journal of Experimental Medicine, Vol. 178, No. 6, 01.12.1993, p. 2165-2172.

Research output: Contribution to journalArticle

Imani, Farhad ; Horii, Yasuhiro ; Suthanthiran, Manikkam ; Skolnik, Edward Y. ; Makita, Zenji ; Sharma, Vijay ; Sehajpal, Prabodh ; Vlassara, Helen. / Advanced glycosylation endproduct-specific receptors on human and rat t-lymphocytes mediate synthesis of interferon γ : Role in tissue remodeling. In: Journal of Experimental Medicine. 1993 ; Vol. 178, No. 6. pp. 2165-2172.
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AU - Skolnik, Edward Y.

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AU - Sharma, Vijay

AU - Sehajpal, Prabodh

AU - Vlassara, Helen

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