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Title: Theophylline and adenosine modulate the inflammatory functions of the human neutrophil by exerting an opposing influence on the stimulus-induced increase in intracellular calcium

Abstract

Based on evidence that endogenously-produced adenosine inhibited neutrophil responses, the influence of methylxanthine bronchodilators on neutrophil responses stimulated in vitro by n-formyl-methionyl-leucyl-phenylalanine (fMLP) was examined. At concentrations between 10/sup /minus/5/ M and 10/sup /minus/4/ M, theophylline potentiated lysosomal enzyme release by 30 to 50%, superoxide anion formation by 30 to 60%, and neutrophil aggregation. Theophylline at concentrations >10/sup /minus/4/ M inhibited the same responses by >90%. Adenosine deaminase mimicked, whereas adenosine reversed the theophylline potentiation. A potential role for calcium in the modulation of the neutrophil responses by theophylline and adenosine was explored. Theophylline enhanced by >150% the fMLP-stimulated increase in cytoplasmic calcium concentration ((Ca/sup 2 +/)/sub i/) at time points between 5 and 90 sec as measured by Fura-2. Adenosine deaminase induced a comparable enhancement, whereas 3 /times/ 10/sup /minus/7/ M adenosine and 10/sup /minus/7/ M N-ethylcarboxamideadenosine decreased the (Ca/sup 2 +/)/sub i/ in fMLP-stimulated neutrophils. Extracellular calcium was not required for the opposing influences of theophylline and adenosine and neither compound altered fMLP-stimulated /sup 45/Ca uptake at the early time points.

Authors:
Publication Date:
Research Org.:
Rush Univ., Chicago, IL (USA). Graduate Coll. of Nursing
OSTI Identifier:
5904999
Resource Type:
Thesis/Dissertation
Resource Relation:
Other Information: Thesis (Ph. D.)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ADENOSINE; BIOLOGICAL EFFECTS; CALCIUM COMPOUNDS; BIOSYNTHESIS; NEUTROPHILS; BIOLOGICAL FUNCTIONS; VASODILATORS; CALCIUM 45; HYDROLASES; INHIBITION; MAN; TRACER TECHNIQUES; ALKALINE EARTH ISOTOPES; ALKALINE EARTH METAL COMPOUNDS; ANIMALS; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY FLUIDS; CALCIUM ISOTOPES; CARDIOVASCULAR AGENTS; DAYS LIVING RADIOISOTOPES; DRUGS; ENZYMES; EVEN-ODD NUCLEI; FUNCTIONS; INTERMEDIATE MASS NUCLEI; ISOTOPE APPLICATIONS; ISOTOPES; LEUKOCYTES; MAMMALS; MATERIALS; NUCLEI; NUCLEOSIDES; NUCLEOTIDES; ORGANIC COMPOUNDS; PRIMATES; RADIOISOTOPES; RIBOSIDES; SYNTHESIS; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Schmeichel Morley, C.J. Theophylline and adenosine modulate the inflammatory functions of the human neutrophil by exerting an opposing influence on the stimulus-induced increase in intracellular calcium. United States: N. p., 1988. Web.
Schmeichel Morley, C.J. Theophylline and adenosine modulate the inflammatory functions of the human neutrophil by exerting an opposing influence on the stimulus-induced increase in intracellular calcium. United States.
Schmeichel Morley, C.J. Fri . "Theophylline and adenosine modulate the inflammatory functions of the human neutrophil by exerting an opposing influence on the stimulus-induced increase in intracellular calcium". United States. doi:.
@article{osti_5904999,
title = {Theophylline and adenosine modulate the inflammatory functions of the human neutrophil by exerting an opposing influence on the stimulus-induced increase in intracellular calcium},
author = {Schmeichel Morley, C.J.},
abstractNote = {Based on evidence that endogenously-produced adenosine inhibited neutrophil responses, the influence of methylxanthine bronchodilators on neutrophil responses stimulated in vitro by n-formyl-methionyl-leucyl-phenylalanine (fMLP) was examined. At concentrations between 10/sup /minus/5/ M and 10/sup /minus/4/ M, theophylline potentiated lysosomal enzyme release by 30 to 50%, superoxide anion formation by 30 to 60%, and neutrophil aggregation. Theophylline at concentrations >10/sup /minus/4/ M inhibited the same responses by >90%. Adenosine deaminase mimicked, whereas adenosine reversed the theophylline potentiation. A potential role for calcium in the modulation of the neutrophil responses by theophylline and adenosine was explored. Theophylline enhanced by >150% the fMLP-stimulated increase in cytoplasmic calcium concentration ((Ca/sup 2 +/)/sub i/) at time points between 5 and 90 sec as measured by Fura-2. Adenosine deaminase induced a comparable enhancement, whereas 3 /times/ 10/sup /minus/7/ M adenosine and 10/sup /minus/7/ M N-ethylcarboxamideadenosine decreased the (Ca/sup 2 +/)/sub i/ in fMLP-stimulated neutrophils. Extracellular calcium was not required for the opposing influences of theophylline and adenosine and neither compound altered fMLP-stimulated /sup 45/Ca uptake at the early time points.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Fri Jan 01 00:00:00 EST 1988},
month = {Fri Jan 01 00:00:00 EST 1988}
}

Thesis/Dissertation:
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