Skip to main content
main-content

01.12.2015 | Research article | Ausgabe 1/2015 Open Access

BMC Pulmonary Medicine 1/2015

No evidence for altered intracellular calcium-handling in airway smooth muscle cells from human subjects with asthma

Zeitschrift:
BMC Pulmonary Medicine > Ausgabe 1/2015
Autoren:
David Sweeney, Fay Hollins, Edith Gomez, Rajendra Mistry, Ruth Saunders, Robert Alfred John Challiss, Christopher Edward Brightling
Wichtige Hinweise
David Sweeney and Fay Hollins contributed equally to this work.

Competing interests

CE Brightling serves on advisory boards for GlaxoSmithKline, AstraZeneca, MedImmune, Roche, and Aerovance; receives honoraria from Novartis; and receives research support from GlaxoSmithKline, AstraZeneca, and MedImmune. The rest of the authors have declared that they have no competing interests.

Authors’ contributions

DS carried out the intracellular calcium measurement and calcium uncaging assays, participated in the experimental design, data analysis and drafted the manuscript. FH carried out the intracellular calcium measurement and collagen gel assays, participated in the experimental design, data analysis and drafted the manuscript. EG carried out the SERCA2 measurement and data analysis. RM carried out the IP3 accumulation assays and data analysis. RS participated in data analysis. RAJC conceived the study, participated in the design and data analysis, and drafted the manuscript. CEB conceived the study, participated in the design and data analysis, and drafted the manuscript. All authors read and approved the final manuscript.

Abstract

Background

Asthma is characterized by airway hyper-responsiveness and variable airflow obstruction, in part as a consequence of hyper-contractile airway smooth muscle, which persists in primary cell culture. One potential mechanism for this hyper-contractility is abnormal intracellular Ca2+ handling.

Methods

We sought to compare intracellular Ca2+ handling in airway smooth muscle cells from subjects with asthma compared to non-asthmatic controls by measuring: i) bradykinin-stimulated changes in inositol 1,4,5-trisphosphate (IP3) accumulation and intracellular Ca2+ concentration, ii) sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) expression, iii) mechanisms of cytoplasmic Ca2+ clearance assessed following instantaneous flash photolytic release of Ca2+ into the cytoplasm.

Results

We found no differences in airway smooth muscle cell basal intracellular Ca2+ concentrations, bradykinin-stimulated IP3 accumulation or intracellular Ca2+ responses. Quantification of SERCA2 mRNA or protein expression levels revealed no differences in ASM cells obtained from subjects with asthma compared to non-asthmatic controls. We did not identify differences in intracellular calcium kinetics assessed by flash photolysis and calcium uncaging independent of agonist-activation with or without SERCA inhibition. However, we did observe some correlations in subjects with asthma between lung function and the different cellular measurements of intracellular Ca2+ handling, with poorer lung function related to increased rate of recovery following flash photolytic elevation of cytoplasmic Ca2+ concentration.

Conclusions

Taken together, the experimental results reported in this study do not demonstrate major fundamental differences in Ca2+ handling between airway smooth muscle cells from non-asthmatic and asthmatic subjects. Therefore, increased contraction of airway smooth muscle cells derived from asthmatic subjects cannot be fully explained by altered Ca2+ homeostasis.
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 1/2015

BMC Pulmonary Medicine 1/2015 Zur Ausgabe

Neu im Fachgebiet Innere Medizin

Meistgelesene Bücher aus der Inneren Medizin

2017 | Buch

Rheumatologie aus der Praxis

Entzündliche Gelenkerkrankungen – mit Fallbeispielen

Dieses Fachbuch macht mit den wichtigsten chronisch entzündlichen Gelenk- und Wirbelsäulenerkrankungen vertraut. Anhand von über 40 instruktiven Fallbeispielen werden anschaulich diagnostisches Vorgehen, therapeutisches Ansprechen und der Verlauf …

Herausgeber:
Rudolf Puchner

2016 | Buch

Ambulant erworbene Pneumonie

Was, wann, warum – Dieses Buch bietet differenzierte Diagnostik und Therapie der ambulant erworbenen Pneumonie zur sofortigen sicheren Anwendung. Entsprechend der neuesten Studien und Leitlinien aller wichtigen Fachgesellschaften.

Herausgeber:
Santiago Ewig

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Innere Medizin und bleiben Sie gut informiert – ganz bequem per eMail.

© Springer Medizin 

Bildnachweise