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Heimo Mairbäurl, PhD Research Interests Effects of hypoxia and inflammation on alveolar epithelial barrier function Beta-‐adrenergic signaling Interaction between alveolar macrophages, epithelium and endothelium Control of cellular metabolism in hypoxia
Short CV Affiliation Mairbäurl, Heimo apl.Professor of Physiology Medical Clinic VII, Sports Medicine University of Heidelberg Im Neuenheimer Feld 410 69120 Heidelberg Phone: +49 6221 56 -‐8103 FAX: +49 6221 56 -‐7307 E-‐mail: [email protected]‐heidelberg.de Homepage: http://www.klinikum.uni-‐heidelberg.de/Ionentransport.113874.0.html Curriculum Vitae 1972-‐ Study of Biology, University of Innsbruck, Austria 1978 Graduation to PhD from the Department of Physiology, University of Innsbruck 1978-‐1982 Postdoc at the Department of Physiology, University of Innsbruck, Austria 1982-‐1983 Visiting Scholar at the Department of Hematology, Harbor UCLA Medical Center,
Torrance, California, USA 1983-‐1987 Research Assistant, Department of Physiology, University of Innsbruck, Austria 1987-‐1991 Associate Research Scientist, Department of Cellular and Molecular Physiology,
Yale University Medical School, New Haven, CT, USA 1991-‐ present Senior Scientist, Medical Clinic VII, Sports Medicine, University of Heidelberg,
Germany Honors & Awards 1993 Habilitation for Applied Physiology, Medical Clinic VII, Sports Medicine,
University of Heidelberg, Germany 1995 adjunct Professorship
Projects The alveolar barrier mediates the diffusion of oxygen and CO2 between alveoli and blood, which is impaired by pulmonary edema. Hypoxia increases alveolar permeability, inhibits epithelial reabsorption, and stimulates macrophages. It also impairs potentially protective mechanisms such as beta-‐2 adrenergic signaling. When stimulated with bacterial toxins alveolar macrophages release mediators (e.g. cytokines, nitric oxide) which also inhibit reabsorption and increase alveolar permeability. Effects of hypoxia and inflammation are additive.
As part of the DLZ-‐pneumonia/acute lung injury/ARDS disease area, we aim to identify signaling mechanisms, by which hypoxia aggravates inflammation-‐induced alveolar damage, and study the role of hypoxia inducible factors (HIF) in the expression of cytokines, NO, and mitochondrial malfunction in alveolar macrophages and alveolar epithelium. Together these factors might increase the formation of reactive oxygen and nitrogen species, which contribute to hypoxic and inflammatory alveolar dysfunction.
Beta-‐2 adrenergics stimulate edema clearance by stimulating activity and expression of alveolar Na-‐transporters, which prevents edema formation. This system is malfunctioning in hypoxia. We study the role of CREB in the expression of Na-‐transporters in the normoxic and test whether altered CREB activity, in a hypoxia/HIF-‐dependent manner, causes the impairment of beta-‐2 adrenergic stimulation of Na-‐transport in the hypoxic alveolar epithelium (funded by DFG).
Funding Federal Ministry for education and research (TLRC-‐H, DLZ/BMBF) German Research Foundation (DFG: Ma 1503/28-‐1) IntenC (BMBF-‐TUBITAK) Team Post-‐doctoral fellows Dr. Emel Baloglu Tel.: +49 6221 56 -‐7810 Email: [email protected]‐heidelberg.de PhD students Kalpana Velineni Tel.: +49 6221 56 -‐7810 Email: [email protected]‐heidelberg.de Technical Assistants Christiane Herth Tel.: +49 6221 56 -‐38110 Email: [email protected]‐heidelberg.de Sonja Engelhardt Tel.: +49 6221 56 -‐38110 Email: [email protected]‐heidelberg.de
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Selected Publications 1. Baloglu E, Ke A, Abu-‐Taha IH, Bärtsch P and Mairbäurl H. In vitro hypoxia impairs beta 2
adrenergic signaling in primary rat alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol 296: L500-‐L509, 2009.
2. Baloglu E, Reingruber T, Bartsch P and Mairbaurl H. beta2-‐Adrenergics in hypoxia desensitize receptors but blunt inhibition of reabsorption in rat lungs. Am J Respir Cell Mol Biol 45: 1059-‐1068, 2011.
3. Dehler M, Zessin E, Bärtsch P and Mairbäurl H. Hypoxia causes permeability edema in the constant-‐pressure perfused rat lung. Eur Respir J 27: 600-‐606, 2006.
4. Faoro V, Fink B, Taudorf S, Dehnert C, Berger MM, Swenson ER, Bailey DM, Bartsch P and Mairbaurl H. Acute in vitro hypoxia and high-‐altitude (4,559 m) exposure decreases leukocyte oxygen consumption. Am J Physiol Regul Integr Comp Physiol 300: R32-‐R39, 2011.
5. Guney S, Schuler A, Ott A, Höschele S, Baloglu E, Bärtsch P and Mairbäurl H. Dexamethasone prevents transport inhibition by hypoxia in rat lung and alveolar epithelial cells by stimulating activity and expression of Na/K-‐ATPase and ENaC. Am J Physiol Lung Cell Mol Physiol 293: L1332-‐L1338, 2007.
6. Heerlein K, Schulze A, Hotz L, Bärtsch P and Mairbäurl H. Hypoxia decreases cellular ATP-‐demand and inhibits mitochondrial respiration of A549 cells. Am J Respir Cell Molec Biol 32: 44-‐51, 2005.
7. Höschele S and Mairbäurl H. Alveolar flooding at high altitude: failure of reabsorption? News Physiol Sci 18: 55-‐59, 2003.
8. Karle C, Gehrig T, Wodopia R, Höschele S, Kreye VAW, Katus HA, Bärtsch P and Mairbäurl H. Hypoxia-‐induced inhibition of whole cell membrane currents and ion transport of A549 cells. Am J Physiol Lung Cell Molec Physiol 286: L1154-‐L1160, 2004.
9. Loeh B, Baloglu E, Ke A, Bärtsch P and Mairbäurl H. β2-‐adrenergic stimulation blunts inhibition of epithelial ion-‐transport by hypoxia of rat alveolar epithelial cells. Cell Physiol Biochem 25: 123-‐134, 2010.
10. Maggiorini M, Brunner-‐La Rocca H, Peth S, Fischler M, Böhm T, Bernheim A, Kiencke S, Bloch KE, Dehnert C, Naeije R, Lehmann T, Bärtsch P and Mairbäurl H. Both tadalafil and dexamethasone may reduce the incidence of high-‐altitude pulmonary edema. Annals of Internal Medicine 145: 497-‐506, 2006.
11. Mairbäurl H. Role of alveolar epithelial sodium transport in high altitude pulmonary edema (HAPE). Respir Physiol Neurobiol 151: 178-‐191, 2006.
12. Mairbäurl H, Weymann J, Möhrlein A, Swenson ER, Maggiorini M, Gibbs JSR and Bärtsch P. Nasal epithelium potential difference at high altitude (4559 m): evidence for secretion. Am J Respir Crit Care Med 167: 862-‐867, 2003.
13. Peth S, Karle C, Dehnert C, Bartsch P and Mairbäurl H. K+ channel activation with minoxidil stimulates nasal-‐epithelial ion transport and blunts exaggerated hypoxic pulmonary hypertension. High Alt Med Biol 7: 54-‐63, 2006.
14. Schmitt L, Wiebel M, Frese F, Dehnert C, Zugck C, Bartsch P and Mairbaurl H. Exercise reduces airway sodium ion reabsorption in cystic fibrosis but not in exercise asthma. Eur Respir J 37: 342-‐348, 2011.
