The circulating neutrophil has three major tasks that it must accomplish before it can carry out its final task of phagocytosis. First, it must deform and flow through the capillaries often while in a stimulated state. Second, it must recognize sites of inflammation in the post- capillary venules and rapidly attach to these sites by rolling and then firmly adhering to the endothelial cells that line the walls of these venules. Finally, it must migrate through the vessel wall and into the surrounding tissue by a continuous process of adhesion and detachment. Our work seeks to address fundamental questions about how neutrophils when stimulated become rigid, aggregate and disaggregate, adhere and detach and migrate: What are the neutrophil's cortical tension and viscosity and how do they change when stimulated and how do these changes influence the neutrophil's ability to move through the small capillaries of the body? What are the fundamental bond forces between the antigens on the unstimulated and stimulated neutrophil and their ligands and antibodies? How do the basic rates of actin polymerization and depolymerization control the motility of neutrophils? We study individual neutrophils from a drop of blood or cells isolated from a small quantity of blood drawn by venipuncture. Fresh venous blood samples drawn into K2EDTA or Na-Citrate vacutainers from healthy donors are isolated from a Ficoll-Hypaque, double density gradient and resuspended in 50% plasma and Hanks' balanced salt solution. Experiments are done with a glass micropipet, which serves as a fundamental, in-vitro model of a capillary vessel. Driving pressures, forces and chemical environments are precisely controlled and deformations and velocities are measured. This permits the mechanical characteristics of the cell, such as cortical tension, viscosity, stiffening due to activation, adhesion due to chemical bond formation, detachment due to the failure of chemical bonds and polymerization due to mechanical and chemical stimulation, to be precisely measured. These studies should provide new information on the mechanical and viscoelastic properties of activated neutrophils, which is important to our basic understanding of infection and inflammation.
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