Chapter 9 - Molecular mechanistic insights on modulation of signal transduction pathways of phospholipase A2 in asthma and chronic obstructive pulmonary disease

Abstract

Phospholipase A2s (PLA2s) belong to a very important superfamily of various enzymes attributed to hydrolysis of the sn-2 fatty acids of cell membrane phospholipids to deliver arachidonic acid. PLA2s are considered the rate-limiting enzyme for the proximate synthesis of leukotrienes and prostaglandins, which are the main mediators of inflammation. Secretory phospholipase A2 (sPLA2) is the extracellular form of this enzyme, found in the tissues of the human body. The catalytic mechanism regarding the inflammatory pathways of sPLA2 is stimulated by a histidine/aspartic acid/calcium complex within the active site. Alteration in the functions of sPLA2, as well as mutations of sPLA2, lead to diseases including asthma and chronic obstructive pulmonary disease, through the production of pro- and antiinflammatory mediators; thereby, it has a great impact on various immuno-competent cells. The inclined rate of mortality, morbidity, and ineffective treatment correlated with the pathogenesis of chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD), as well as asthma has attracted much research interest. The effective treatment strategy is evolved to determine structure-function relationship of the mutations of sPLA2 for the management of these diseases.