Endothelial catabolism of extracellular adenosine during hypoxia: the role of surface adenosine deaminase and CD26.
نویسندگان
چکیده
Extracellular levels of adenosine increase during hypoxia. While acute increases in adenosine are important to counterbalance excessive inflammation or vascular leakage, chronically elevated adenosine levels may be toxic. Thus, we reasoned that clearance mechanisms might exist to offset deleterious influences of chronically elevated adenosine. Guided by microarray results revealing induction of endothelial adenosine deaminase (ADA) mRNA in hypoxia, we used in vitro and in vivo models of adenosine signaling, confirming induction of ADA protein and activity. Further studies in human endothelia revealed that ADA-complexing protein CD26 is coordinately induced by hypoxia, effectively localizing ADA activity at the endothelial cell surface. Moreover, ADA surface binding was effectively blocked with glycoprotein 120 (gp120) treatment, a protein known to specifically compete for ADA-CD26 binding. Functional studies of murine hypoxia revealed inhibition of ADA with deoxycoformycin (dCF) enhances protective responses mediated by adenosine (vascular leak and neutrophil accumulation). Analysis of plasma ADA activity in pediatric patients with chronic hypoxia undergoing cardiac surgery demonstrated a 4.1 +/- 0.6-fold increase in plasma ADA activity compared with controls. Taken together, these results reveal induction of ADA as innate metabolic adaptation to chronically elevated adenosine levels during hypoxia. In contrast, during acute hypoxia associated with vascular leakage and excessive inflammation, ADA inhibition may serve as therapeutic strategy.
منابع مشابه
Endothelial Catabolism of Extracellular Adenosine during Hypoxia: Role of Surface Adenosine Deaminase and CD26 Inaugural-Dissertation zur Erlangung des Doktorgrades
متن کامل
Physiological role of adenosine and its receptors in tissue hypoxia-induced
It is well known that the metabolic factors play an important role in the regulation of angiogenesis. Increased metabolic activity leads to decreased oxygen levels and causes tissue hypoxia. Hypoxia starts different signals to stimulate angiogenesis and promotes oxygen delivery to tissues. It has been suggested that released adenosine from hypoxic tissues plays a vital role in angiogenesis. ...
متن کاملEndothelial Catabolism of Extracellular Adenosine during Hypoxia: Role of Surface Adenosine Deaminase and CD26
(4939 articles) Immunobiology (2497 articles) Hemostasis, Thrombosis, and Vascular Biology Articles on similar topics can be found in the following Blood collections http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#repub_requests Information about reproducing this article in parts or in its entirety may be found online at: http://bloodjournal.hematologylibrary.org/site/mis...
متن کاملP-142: Adenosine Deaminase Activity during Menses, Follicular and Luteal Phases of Menstrual Cycle
Background: In recent years, numerous regulators of gonadal function have been studied. Adenosine deaminase(ADA) is widely distributed throughout human tissues and may contribute in the regulation of menstrual cycle. The purpose of this study was to determine the plasma activities of total adenosine deaminase (ADAT), and its isoenzymes, ADA1 and ADA2, and ADA1/ADA2 ratio during the menses, foll...
متن کاملCytokines regulate membrane adenosine deaminase on human activated lymphocytes.
CD26 is a lymphocyte marker that can anchor adenosine deaminase (ADA) on the T cell surface. We found that ADA is regulated by cytokines on the cell surface during T cell activation. By means of flow cytometry, immunofluorescence, and immunoblotting techniques, we found that interleukin (IL)-2 and IL-12 up-regulate ecto-ADA and CD26 expression. In clear contrast, IL-4 led to down-regulation of ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Blood
دوره 108 5 شماره
صفحات -
تاریخ انتشار 2006