The long-term objectives of this proposal are to understand the mechanisms of neutrophil emigration across the pulmonary endothelium at cellular and molecular levels. Neutrophil activation and emigration underlie many acute inflammatory processes such as pneumonia. The working hypothesis of this proposal is that neutrophil adhesion to cytokine-activated pulmonary microvascular endothelial cells (ECs) induces changes in the biomechanical properties of ECs, as well as neutrophils. These changes in the biomechanical properties are associated with F-actin rearrangement and/or actin/myosin-mediated contraction in ECs. To test this hypothesis, the proposed studies will first determine the roles of ICAM-1 and E-selectin in mediating the changes in the biomechanical properties of neutrophils and ECs during neutrophil adhesion. Second, the proposal will determine the second messenger cascades involved in initiating the changes in the biomechanical properties of these two cell types induced by adhesion. Third, the proposal will determine if the F-actin cytoskeleton is involved in mediating these changes in biomechanical properties and to identify actin binding proteins involved.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL010177-03
Application #
6183695
Study Section
Lung Biology and Pathology Study Section (LBPA)
Project Start
2000-05-01
Project End
Budget Start
2000-05-01
Budget End
2001-04-30
Support Year
3
Fiscal Year
2000
Total Cost
$39,232
Indirect Cost
Name
Case Western Reserve University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106