Abstract

This is a second revision of a competitive renewal to test the hypothesis that the membrane skeleton is an integral structural component of the PMN microbicidal oxidase system and, hence, plays a critical role in assembly of the NADPH-dependent oxidase of human neutrophils. To this end, the proposed studies will address two specific aims: 1) identification of domains of the cytosolic oxidase component p47phox which mediate assembly of the oxidase; and 2) identification of components of the membrane skeleton associated with the assembled oxidase. It is suggested that results from these studies will provide insights concerning the structural determinants which integrate the assembly of an active oxidase with reorganization of the cytoskeleton during PMN stimulation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI034879-10
Application #
2004004
Study Section
Special Emphasis Panel (ZRG5-BM-1 (01))
Project Start
1988-09-30
Project End
2000-11-30
Budget Start
1996-12-01
Budget End
1997-11-30
Support Year
10
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
University of Iowa
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242

  Publications

Essin, Kirill; Gollasch, Maik; Rolle, Susanne et al. (2009) BK channels in innate immune functions of neutrophils and macrophages. Blood 113:1326-31
Moreland, Jessica G; Hook, Jessica S; Bailey, Gail et al. (2009) Francisella tularensis directly interacts with the endothelium and recruits neutrophils with a blunted inflammatory phenotype. Am J Physiol Lung Cell Mol Physiol 296:L1076-84
Lee, Jimmy S; Nauseef, William M; Moeenrezakhanlou, Alireza et al. (2007) Monocyte p110alpha phosphatidylinositol 3-kinase regulates phagocytosis, the phagocyte oxidase, and cytokine production. J Leukoc Biol 81:1548-61
Zhu, Yanmin; Marchal, Christophe C; Casbon, Amy-Jo et al. (2006) Deletion mutagenesis of p22phox subunit of flavocytochrome b558: identification of regions critical for gp91phox maturation and NADPH oxidase activity. J Biol Chem 281:30336-46
Painter, Richard G; Valentine, Vincent G; Lanson Jr, Nicholas A et al. (2006) CFTR Expression in human neutrophils and the phagolysosomal chlorination defect in cystic fibrosis. Biochemistry 45:10260-9
Femling, Jon K; Cherny, Vladimir V; Morgan, Deri et al. (2006) The antibacterial activity of human neutrophils and eosinophils requires proton channels but not BK channels. J Gen Physiol 127:659-72
Hunt, Catherine L; Nauseef, William M; Weiss, Jerrold P (2006) Effect of D-alanylation of (lipo)teichoic acids of Staphylococcus aureus on host secretory phospholipase A2 action before and after phagocytosis by human neutrophils. J Immunol 176:4987-94
Simons, Mark P; Nauseef, William M; Griffith, Thomas S et al. (2006) Neisseria gonorrhoeae delays the onset of apoptosis in polymorphonuclear leukocytes. Cell Microbiol 8:1780-90
Barker, Jason H; Weiss, Jerrold; Apicella, Michael A et al. (2006) Basis for the failure of Francisella tularensis lipopolysaccharide to prime human polymorphonuclear leukocytes. Infect Immun 74:3277-84
Simons, Mark P; Nauseef, William M; Apicella, Michael A (2005) Interactions of Neisseria gonorrhoeae with adherent polymorphonuclear leukocytes. Infect Immun 73:1971-7

Showing the most recent 10 out of 26 publications