Abstract

The long-term objective of this project is to elucidate the role(s) of sickle red blood cells (SRBC) - endothelial cell (EC) - polymorphonuclear cell (PMN) interactions in sickle cell related acute lung injury The investigators further propose to investigate the potential role of PMN activation in initiating pulmonary microvascular occlusion by the SRBC. To achieve these objectives, the isolated-perfused rat lung model will be used with emphasis on the relationship of prolonged hypoxia with reoxygenation and ischemia (no flow, no ventilation) - reperfusion on initiating microvascular occlusion through mechanism which activate the intact vascular endothelium through the release of various cytokines such as IL-1, TNFalpha, and enhanced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). In this proposal the investigators suggest the PMN is key in causing EC damage as associated with increased permeability edema and enhanced SRBC adhesogenicity to the vascular endothelium. SRBC adhesion/retention will be assessed using Cr51-labeled SRBC. Permeability edema will be used using the capillary filtration coefficient. Studies of the nature proposed will further the understanding in non-infectious causes of sickle acute lung injury.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Comprehensive Center (P60)
Project #
5P60HL038639-12
Application #
6109868
Study Section
Project Start
1999-04-01
Project End
2000-03-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
12
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of South Alabama
Department
Type
DUNS #
City
Mobile
State
AL
Country
United States
Zip Code
36688

  Publications

Pace, B S; Qian, X; Ofori-Acquah, S F (2004) Selective inhibition of beta-globin RNA transcripts by antisense RNA molecules. Cell Mol Biol (Noisy-le-grand) 50:43-51
Haynes Jr, Johnson; Baliga, B Surendra; Obiako, Boniface et al. (2004) Zileuton induces hemoglobin F synthesis in erythroid progenitors: role of the L-arginine-nitric oxide signaling pathway. Blood 103:3945-50
Haynes Jr, Johnson; Obiako, Boniface (2002) Activated polymorphonuclear cells increase sickle red blood cell retention in lung: role of phospholipids. Am J Physiol Heart Circ Physiol 282:H122-30
Foley, Heather A; Ofori-Acquah, Solomon F; Yoshimura, Akihiko et al. (2002) Stat3 beta inhibits gamma-globin gene expression in erythroid cells. J Biol Chem 277:16211-9
Abraham, Ann; Bencsath, F Aladar; Shartava, Archil et al. (2002) Preparation of irreversibly sickled cell beta-actin from normal red blood cell beta-actin. Biochemistry 41:292-6
Kakhniashvili, D G; Goodman, S R (2001) Isolation of spectrin subunits by reverse-phase high-performance liquid chromatography. Protein Expr Purif 23:249-51
Sangerman, J; Kakhniashvili, D; Brown, A et al. (2001) Spectrin ubiquitination and oxidative stress: potential roles in blood and neurological disorders. Cell Mol Biol Lett 6:607-36
Yang, Y M; Pace, B (2001) Pharmacologic induction of fetal hemoglobin synthesis: cellular and molecular mechanisms. Pediatr Pathol Mol Med 20:87-106
Carson, J A; Fillmore, R A; Schwartz, R J et al. (2000) The smooth muscle gamma-actin gene promoter is a molecular target for the mouse bagpipe homologue, mNkx3-1, and serum response factor. J Biol Chem 275:39061-72
Martin, J B; Young, J L; Benoit, J N et al. (2000) Gene transfer to intact mesenteric arteries by electroporation. J Vasc Res 37:372-80

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