Device and method for analysis of blood components and identifying inhibitors and promoters of the inflammatory response

摘要

The present invention provides in vitro models of the in vivo rolling and arrest of leukocytes along the endothelial cell wall, which are important steps in the migration of leukocytes out of the blood stream and into tissue, as part of the inflammatory response. The in vitro models of the invention are functional under physiologic flow conditions resulting in physiologic shear stresses. In a specific embodiment, for modelling leukocyte rolling, the apparatus of the invention comprises a solid phase surface with rolling mediator molecules present thereon. Such rolling mediators are, for example, selectins and selectin ligands which have binding partners expressed on leukocytes. In another specific embodiment, for modelling leukocyte rolling followed by adhesion/arrest, the apparatus of the invention comprises a solid phase surface with both rolling mediators and integrin binding partners present thereon. The apparatuses of the invention can be used for collecting, concentrating, purifying, and analyzing blood and blood components, in particular, leukocytes and subsets thereof. The invention further relates to methods for identifying inhibitors or, alternatively, promoters (agonists, functional components) of the inflammatory response. Therapeutic and diagnostic methods, pharmaceutical compositions and kits are also provided.