| The eosinophil is a granulated leukocyte known to be involved in the pathogenesis of parasitic infections and allergic diseases, such as asthma. Eosinophils are specifically recruited to sites of inflammation and have the capacity to secrete numerous pro-inflammatory molecules along with its toxic granule contents. The eosinophil also expresses two proteins of great interest: lysophospholipases (LPLase) and Charcot-Leyden Crystal protein/galectin-10. The functional roles of the eosinophil LPLases and CLC/gal-10 are examined in this thesis.;A body of evidence has emerged suggesting that the functional component of pulmonary surfactant, dipalmitoyl-phosphatidyicholine (DPPC), is degraded into lysophosphatidylcholine (LPC) and free fatty acid (FFA) during asthmatic exacerbations. This results in loss of the ability of pulmonary surfactant to maintain the patency of the small airways, since neither LPC nor FFA have the ability to reduce surface tension. We hypothesize that the combined activity of secretory phospholipases (sPLA2s) and the eosinophil LPLase activity degrade pulmonary surfactant DPPC, leading to small airway closure in asthma.;CLC/gal-10, a unique member of the galectin family expressed by the eosinophil, basophil, and T regulatory cells. CLC/gal-10 is one of the most abundant proteins in the eosinophil, comprising 7-10% of total cellular protein. Despite the abundance of this protein, little is known about the functional role of this protein in eosinophil biology. Here we show that CLC/gal-10 interacts with eosinophil derived neurotoxin (EDN) and the granule membrane marker CD63. We hypothesize that CLC/gal-10 acts as a chaperone or carrier of the eosinophil cationic proteins during secretion of the eosinophil ribonucleases by piecemeal degranulation. |
