A key component of inflammation is the adhesion of leukocytes to the endothelium in the fluid dynamic environment of the circulation. Unraveling the complex process of leukocyte adhesion to the endothelium will lead to an increased understanding of inflammation and will provide the foundation for the development of novel ways to treat a variety of pathological processes. We will investigate two hypotheses related to leukocyte adhesion to the endothelium. First, we have proposed and found evidence for the hypothesis that beta2 integrin (specifically Mac-1 (CDllb/CD18)) - E-selectin molecular interactions play a role in leukocyte adhesion to the endothelium. These results and our recent studies has led to the following hypothesis: As leukocytes adhere to the endothelium, leukocyte expressed Mac-1 can interact with the endothelium via two distinct mechanisms: one interaction occurring during leukocyte rolling and another interaction occurring during firm adhesion. We will probe this hypothesis by completing the following specific aim.
Specific Aim I : To determine if leukocyte-sized microspheres coated with purified Mac-1 adhere to cytokine activated endothelial cells under physiologically relevant flow conditions through a multi-step process involving at least two distinct mechanisms. Our second hypothesis is that the number of E-selectin ligands expressed by a neutrophil is in significant excess of the number required to support a stable rolling adhesion on the endothelium via E-selectin. We will probe this hypothesis by completing the following specific aim.
Specific Aim II : To determine if the E-selectin ligand density present on neutrophils is in significant excess of that required to support a stable rolling adhesion on cytokine activated human umbilical vein endothelial cells via E-selectin under physiologically relevant flow conditions.
| Kummitha, China Malakondaiah; Shirure, Venktesh S; Delgadillo, Luis F et al. (2012) HECA-452 is a non-function blocking antibody for isolated sialyl Lewis x adhesion to endothelial expressed E-selectin under flow conditions. J Immunol Methods 384:43-50 |
| Benavides, Uruguaysito; Gonzalez-Murguiondo, Mariana; Harii, Norikazu et al. (2010) Phenyl methimazole suppresses dextran sulfate sodium-induced murine colitis. Eur J Pharmacol 643:129-38 |
