Over the past decade, considerable new information about the eosinophil has emerged and its roles in diseases have been elucidated. This information suggests that the eosinophil is a principal mediator of the pathology of bronchial asthma and is a critical participant in certain cutaneous diseases. The recognition that the eosinophil is a critical cell in disease has focused attention on the mechanisms by which eosinophils function in disease. This proposal for an Asthma, Allergic and Immunologic Diseases Cooperative Research Center focuses on the mechanisms by which eosinophils infiltrate tissues and cause damage during hypersensitivity diseases. Three projects address fundamental questions regarding the interactions between eosinophils and endothelial cells, the subsequent migration of the eosinophil through the vessel wall, the stimuli causing eosinophil activation in the extracellular milieu with release of toxic cationic proteins and with elaboration of cytokines, and the mechanisms by which released granule proteins stimulate other cells using the blood platelet as a model. Related clinical questions to be investigated include whether patterns of leukocyte adhesion molecule expression are present in eosinophil- associated diseases, and whether measurement of eosinophil granule proteins in sputum can be correlated with eosinophil infiltration and degranulation in the lung. A coordinated and disciplined approach to these goals is described in which four overlapping teams of investigators will approach these questions in an integrated manner. In addition, three proposals for Demonstration and Education projects are described. Overall, these projects hold the promise of yielding significant novel information about the eosinophil and its roles in diseases.
| Plager, Douglas A; Davis, Mark D P; Andrews, Amy G et al. (2009) Eosinophil ribonucleases and their cutaneous lesion-forming activity. J Immunol 183:4013-20 |
