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.
| Wang, Qin; Pfeiffer 2nd, Gordon R; Stevens, Troy et al. (2002) Lung microvascular and arterial endothelial cells differ in their responses to intercellular adhesion molecule-1 ligation. Am J Respir Crit Care Med 166:872-7 |
| Wang, Qin; Doerschuk, Claire M (2002) The signaling pathways induced by neutrophil-endothelial cell adhesion. Antioxid Redox Signal 4:39-47 |
| Wang, Q; Doerschuk, C M (2001) The p38 mitogen-activated protein kinase mediates cytoskeletal remodeling in pulmonary microvascular endothelial cells upon intracellular adhesion molecule-1 ligation. J Immunol 166:6877-84 |
| Wang, Q; Chiang, E T; Lim, M et al. (2001) Changes in the biomechanical properties of neutrophils and endothelial cells during adhesion. Blood 97:660-8 |
