Department / Division
Medicine /
Medicine-Pulmonary
Address
DUMC 103003
Durham, NC 27710
106 Research Drive
Durham, NC 27710
Appointment Telephone
Not accepting new patients
Office Telephone
919-668-7762 (Duke),
919-286-6946 (Durham VA)
Fax Telephone
919-416-5847, 919-684-5266
Clinical Interests
Pulmonary, critical care medicine
Research Interests
The McMahon Lab at Duke University and Durham VA Medical Center is investigating novel roles of the red blood cell (RBC) in the circulation. The regulated release of the vasodilator SNO (a form of NO, nitric oxide) by RBCs within the respiratory cycle in mammals optimizes nutrient delivery at multiple levels, especially in the lung (gas exchange) and the peripheral microcirculation (O2 transport to tisses). Deficiency of RBC SNO bioactivity (as in human RBCs banked for transfusion), for example, appears to contribute to the serious lung and circulatory problems associated with RBC transfusion in some settings. We have also demonstrated benefit in the use of treatments that exploit RBCs as a vehicle for delivery of SNOs, in both human patients and in model animals.
RBCs also release ATP in response to stimuli including deformation and hypoxia, and the exported ATP also participates in the maintenance of a healthy circulation, according to mechanisms that we are now unraveling.
We use basic and translational approaches to understand the molecular mechanisms by which these RBC-derived signals effect circulatory changes in human health and disease, particularly in the lung. Disease states driving this research include acute and chronic lung diseases such as transfusion-related respiratory problems, sickle cell disease, and pulmonary hypertension of adults and newborns.
Funding: VA and NIH.
This faculty member has no reported relationships with industry.
Representative Publications
Torok, JA; Brahmajothi, MV; Zhu, H; Tinch, BT; Auten, RL; McMahon, TJ. Transpulmonary flux of S-nitrosothiols and pulmonary vasodilation during nitric oxide inhalation: role of transport. American Journal of Respiratory Cell and Molecular Biology. 2012;47:37-43.
(2012)
Abstract
Zhu, H; Zennadi, R; Xu, BX; Eu, JP; Torok, JA; Telen, MJ; McMahon, TJ. Impaired adenosine-5'-triphosphate release from red blood cells promotes their adhesion to endothelial cells: a mechanism of hypoxemia after transfusion. Critical Care Medicine. 2011;39:2478-2486.
(2011)
Abstract
Bennett-Guerrero, E; Veldman, TH; Doctor, A; Telen, MJ; Ortel, TL; Reid, TS; Mulherin, MA; Zhu, H; Buck, RD; Califf, RM; McMahon, TJ. Evolution of adverse changes in stored RBCs. Proceedings of the National Academy of Sciences of USA. 2007;104:17063-17068.
(2007)
Abstract
Sonveaux, P; Lobysheva, II; Feron, O; McMahon, TJ. Transport and peripheral bioactivities of nitrogen oxides carried by red blood cell hemoglobin: role in oxygen delivery. Physiology. 2007;22:97-112.
(2007)
Abstract
Du, W; McMahon, TJ; Zhang, ZS; Stiber, JA; Meissner, G; Eu, JP. Excitation-contraction coupling in airway smooth muscle. Journal of Biological Chemistry. 2006;281:30143-30151.
(2006)
Abstract
McMahon, TJ; Doctor, A. Extrapulmonary effects of inhaled nitric oxide: role of reversible S-nitrosylation of erythrocytic hemoglobin. Proceedings of the American Thoracic Society. 2006;3:153-160.
(2006)
Abstract
McMahon, TJ; Ahearn, GS; Moya, MP; Gow, AJ; Huang, YC; Luchsinger, BP; Nudelman, R; Yan, Y; Krichman, AD; Bashore, TM; Califf, RM; Singel, DJ; Piantadosi, CA; Tapson, VF; Stamler, JS. A nitric oxide processing defect of red blood cells created by hypoxia: deficiency of S-nitrosohemoglobin in pulmonary hypertension. Proceedings of the National Academy of Sciences of USA. 2005;102:14801-14806.
(2005)
Abstract
Foster, MW; McMahon, TJ; Stamler, JS. S-nitrosylation in health and disease. Trends in Molecular Medicine. 2003;9:160-168.
(2003)
Abstract
McMahon, TJ. Hemoglobin and nitric oxide. New England Journal of Medicine. 2003;349:402-405.
(2003)
Abstract
McMahon, TJ; Moon, RE; Luschinger, BP; Carraway, MS; Stone, AE; Stolp, BW; Gow, AJ; Pawloski, JR; Watke, P; Singel, DJ; Piantadosi, CA; Stamler, JS. Nitric oxide in the human respiratory cycle. Nature Medicine. 2002;8:711-717.
(2002)
Abstract
McMahon, TJ; Exton Stone, A; Bonaventura, J; Singel, DJ; Solomon Stamler, J. Functional coupling of oxygen binding and vasoactivity in S-nitrosohemoglobin. Journal of Biological Chemistry. 2000;275:16738-16745.
(2000)
Abstract
McMahon, TJ; Stamler, JS. Concerted nitric oxide/oxygen delivery by hemoglobin. Methods in Enzymology. 1999;301:99-114.
(1999)
Abstract
McMahon, TJ; Ignarro, LJ; Kadowitz, PJ. Influence of Zaprinast on vascular tone and vasodilator responses in the cat pulmonary vascular bed. Journal of Applied Physiology. 1993;74:1704-1711.
(1993)
Abstract
McMahon, TJ; Hood, JS; Kadowitz, PJ. Pulmonary vasodilator response to vagal stimulation is blocked by N omega-nitro-L-arginine methyl ester in the cat. Circulation Research. 1992;70:364-369.
(1992)
Abstract
McMahon, TJ; Hood, JS; Bellan, JA; Kadowitz, PJ. N omega-nitro-L-arginine methyl ester selectively inhibits pulmonary vasodilator responses to acetylcholine and bradykinin. Journal of Applied Physiology. 1991;71:2026-2031.
(1991)
Abstract
