Allergen-induced airway hyperresponsiveness is absent in ecto-5 '-nucleotidase (CD73)-deficient mice

Schreiber, Rainer and Castrop, Hayo and Kunzelmann, Karl (2008) Allergen-induced airway hyperresponsiveness is absent in ecto-5 '-nucleotidase (CD73)-deficient mice. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 457 (2). pp. 431-440. ISSN 0031-6768, 1432-2013

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Abstract

Adenosine is formed from extracellular purines by ecto-5'-nucleotidase (CD73) and is an essential player in allergic airway inflammation. The contribution of adenosine and other purines to electrolyte transport and mucociliary clearance was studied in airways of allergen challenged mice. No signs for allergen-induced inflammation were found in CD73-/- mice, and adenosine monophosphate (AMP) was unable to elicit airway Cl- secretion in these animals. Tracheas of ovalbumin (OVA)-treated BALB/c and CD73+/+ mice were hyperresponsive towards methacholine when assessed by Penh and direct optical measurement of contraction. In addition Cl- secretion activated by ATP and ADP was enhanced. These changes were not observed in CD73-/- mice. Expression of CFTR or CLCA was unchanged upon OVA treatment of CD73 mice, suggesting enhanced Cl- secretion due to upregulated purinergic pathways. Mucociliary clearance was determined by measuring particle transport in excised mouse tracheas and was strongly enhanced in OVA-challenged CD73+/+ mice, but remained unchanged in CD73-/- mice. While mucociliary clearance is activated by allergen exposure independent of functional ecto-5'-nucleotidase, airway inflammation is largely dependent on CD73. Thus, ecto5'-nucleotidase may provide a novel target for therapeutic intervention, probably by local application of ecto-5'-nucleotidase inhibitors through inhalation.

Item Type: Article
Uncontrolled Keywords: OBSTRUCTIVE PULMONARY-DISEASE; INFLAMMATION; ADENOSINE; ASTHMA; ATP; RESPONSIVENESS; NUCLEOTIDES; CLEARANCE; RECEPTORS; CELLS; Ecto-5 '-nucleotidase; CD73; Asthma; Electrolyte transport; Mucociliary clearance; Chloride secretion; Chloride transport; Respiratory epithelia; Airways; P2-purinergic receptor; Adenosine; Adenosine diphosphate (ADP)
Subjects: 500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann
Depositing User: Dr. Gernot Deinzer
Date Deposited: 21 Oct 2020 08:17
Last Modified: 21 Oct 2020 08:17
URI: https://pred.uni-regensburg.de/id/eprint/30137

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