Ether Lipids, Eicosanoids, and Lung Cell Pathophysiology

$1,632,221P01FY2008HLNIH

National Jewish Health, Denver CO

Investigators

Linked publications & trials

Paper 31896171 Paper 28421818 Paper 28280112 Paper 28257233 Paper 27837740 Paper 27501951 Paper 27448436 Paper 27402702 Paper 27095543 Paper 26841868 Paper 26551758 Paper 26386811 Paper 26232173 Paper 26033355 Paper 25838312 Paper 25736244 Paper 25575758 Paper 25498313 Paper 25359381 Paper 25182651 Paper 24367044 Paper 24325577 Paper 24297180 Paper 24182349 Paper 23950842 Paper 23936544 Paper 23883581 Paper 23863635 Paper 23530199 Paper 23451220 Paper 23293064 Paper 23154082 Paper 23108096 Paper 22566847 Paper 22465125 Paper 22393044 Paper 22307908 Paper 22303003 Paper 22220903 Paper 21942646 Paper 21813769 Paper 21782511 Paper 21297111 Paper 21245396 Paper 21205826 Paper 21132278 Paper 20887783 Paper 20805415 Paper 20705608 Paper 20693431 Paper 20643646 Paper 20530831 Paper 20337376 Paper 20226226 Paper 20219673 Paper 19916514 Paper 19548361 Paper 19502385 Paper 19273646 Paper 19176526 Paper 19130898 Paper 19007140 Paper 18952895 Paper 18824544 Paper 18714031 Paper 18550790 Paper 18406359 Paper 18285330 Paper 18083708 Paper 17659880 Paper 17636891 Paper 17548650 Paper 17475884 Paper 17293613 Paper 16814865 Paper 16641135 Paper 16617059 Paper 16407308 Paper 16407295 Paper 16394011 Paper 16384548 Paper 16239148 Paper 16236797 Paper 16115894 Paper 16061942 Paper 15961057 Paper 15716579 Paper 15650405 Paper 15465363 Paper 15316091 Paper 15262974 Paper 15173620 Paper 15096493 Paper 15052324 Paper 15041029 Paper 14963030 Paper 14766753 Paper 14766287 Paper 14676210 Paper 14623879

Abstract

DESCRIPTION (provided by applicant): The goal of this proposal is to study the production and biological roles of lipid mediators in models of inflammation and apoptosis, processes that are inherent components in pulmonary diseases. The four scientific projects bring together complementary approaches to investigate the regulation of eicosanoid production in macrophages during phagocytosis; and to identify unique lipid mediators produced by oxidants and during apoptosis, which act as signals for apoptotic cell recognition by phagocytes. The objectives include: 1) Investigating mechanisms of cPLA2 activation in macrophages during phagocytosis of microorganisms that engage specific pattern recognition receptors; determining the role of cPLA2 in the susceptibility to microbial infection; and studying mechanisms for cPLA2 inactivation by oxidants and caspases during phagocytosis. 2) Studying how the subcellular organization and formation of complexes of downstream enzymes involved in eicosanoid production by macrophages regulates production of eicosanoids from the cyclooxygenase and lipoxygenase pathways. 3) Determining if lyso- and oxidized-phospholipid mediators are produced by apoptotic cells; and elucidating their mechanism of externalization and role as signals for the recruitment, recognition and engulfment by phagocytes. 4) Structural characterization by mass spectrometry of lipid mediators produced from cholesterol, plasmalogen and phosphatidylserine in response to oxidant exposure and during apoptosis. Novel mass spectrometry approaches will be developed to image these lipid mediators in pulmonary tissues. This program brings together investigators with diverse expertise in cell biology, biochemistry, enzymology and structural biology. Multidisciplinary approaches will be used to provide information about the structural identity of lipid mediators, the molecular mechanisms involved in their production, and their biological roles.

View original record on NIH RePORTER →