Normal function of the airway tree is to permit the free flow of gas to an from the alveoli. With inflammation, obstruction of these airways may occur that leads to severe difficulty in breathing or even death. This program project will focus on mechanisms by which allergic inflammation can alter the responsiveness of airways. Although both of these factors have been well studied independently, how they interact remains poorly understood. Inflammation can clearly have several independent and perhaps unrelated influences on the responsiveness of the airways. Of the many possible factors and processes that might be involved in the interaction of airway size and inflammation, we have chosen to focus on several where new insights will likely be obtained. These include the physical interaction between inflamed airways and parenchyma, the inflammatory cell and structural profile induced by specific cytokines regulation of perfusion and inflammatory cell traffic by the airway circulation, and altered neural sensitivity and control. Each project in this program will focus on one or more of these factors addressing several specific aims with state-of-the-art-approaches. Projects and methods span the range from subcellular and molecular approaches to quantitative measurements of airway size in vivo. Projects are tightly interactive with all project leaders serving as co-investigators on other projects, and frequent group meetings. These interactions not only facilitate the progress of work within each project, but they also enhance the development of new ideas and interactions between the projects. In this way the program project function to greatly enhance the productivity of individual progress, thereby making the composite endeavor far greater than the sum of the individual projects. Successful completion of the aims of this tightly integrated program will provide new insights into how airways function in an inflammatory environment.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL010342-36
Application #
6526615
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Noel, Patricia
Project Start
1978-06-01
Project End
2004-08-31
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
36
Fiscal Year
2002
Total Cost
$1,594,290
Indirect Cost
Name
Johns Hopkins University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Han, Liang; Limjunyawong, Nathachit; Ru, Fei et al. (2018) Mrgprs on vagal sensory neurons contribute to bronchoconstriction and airway hyper-responsiveness. Nat Neurosci 21:324-328
Hallowell, R W; Collins, S L; Craig, J M et al. (2017) mTORC2 signalling regulates M2 macrophage differentiation in response to helminth infection and adaptive thermogenesis. Nat Commun 8:14208
Moldobaeva, Aigul; Jenkins, John; Zhong, Qiong et al. (2017) Lymphangiogenesis in rat asthma model. Angiogenesis 20:73-84
Craig, John M; Scott, Alan L; Mitzner, Wayne (2017) Immune-mediated inflammation in the pathogenesis of emphysema: insights from mouse models. Cell Tissue Res 367:591-605
Oh, Min-Hee; Collins, Samuel L; Sun, Im-Hong et al. (2017) mTORC2 Signaling Selectively Regulates the Generation and Function of Tissue-Resident Peritoneal Macrophages. Cell Rep 20:2439-2454
Lagassé, H A Daniel; Anidi, Ifeanyi U; Craig, John M et al. (2016) Recruited monocytes modulate malaria-induced lung injury through CD36-mediated clearance of sequestered infected erythrocytes. J Leukoc Biol 99:659-71
Lin, Amanda H Y; Shang, Yan; Mitzner, Wayne et al. (2016) Aberrant DNA Methylation of Phosphodiesterase [corrected] 4D Alters Airway Smooth Muscle Cell Phenotypes. Am J Respir Cell Mol Biol 54:241-9
Zhong, Qiong; Jenkins, John; Moldobaeva, Aigul et al. (2016) Effector T Cells and Ischemia-Induced Systemic Angiogenesis in the Lung. Am J Respir Cell Mol Biol 54:394-401
Vigeland, Christine L; Collins, Samuel L; Chan-Li, Yee et al. (2016) Deletion of mTORC1 Activity in CD4+ T Cells Is Associated with Lung Fibrosis and Increased ?? T Cells. PLoS One 11:e0163288
D'Alessio, F R; Craig, J M; Singer, B D et al. (2016) Enhanced resolution of experimental ARDS through IL-4-mediated lung macrophage reprogramming. Am J Physiol Lung Cell Mol Physiol 310:L733-46

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