SELECTED ARTICLES FROM THE RECENT LITERATURE 2007

December 19, 2007

Secreted Phospholipase A2 Abnormalities in Asthma

Summary
Phospholipase A2 plays a key role in synthesis of prostaglandins and leukotrienes. It hydrolyzes the sn-2 position of membrane phospholipids, thus liberating unesterified arachidonic acid. Arachidonic acid is the precursor of prostaglandins and leukotrienes. Phospholipase A2 exists in several forms. The major division in phospholipase A2 is the distinction between cytosolic phospholipase A2 and secreted phospholipase A2 enzymes. Cytosolic phospholipase A2 is necessary for efficient eicosanoid biosynthesis. However, a group of secreted phospholipase A2 enzymes coordinate with cytosolic phospholipase A2 to augment synthesis of eicosanoids. Secreted phospholipase A2 cleavage is upregulated by inflammatory cytokines such as interleukin-1 beta. In vitro, secreted phospholipase A2 enzymes are linked to the generation of cysteinyl leukotrienes, whereas cytosolic phospholipase A2 is more closely associated with the production of PGE2 (an "antiinflammatory" eicosanoid).

There are nine functional human secreted phospholipase A2 enzymes. Groups V and X have the highest arachidonic acid releasing activities in assays employing mammalian cells. Secreted phospholipase A2 enzyme activity appears in bronchoalveolar lavage fluid and nasal lavage fluid after allergen challenge.

The authors of this study assessed the expression of the full set of cytosolic and secreted phospholipase A2 enzymes in lower airway cells obtained by induced sputum in subjects with asthma and exercise-induced bronchospasm compared to controls. They found that the level of extracellular secreted phospholipase A2-X protein in the airways increased in response to exercise challenge in the asthma group. They remained unchanged in the nonasthmatic control subjects after exercise, and were lower in nonasthmatics as well. They also found that the highest levels of secreted phospholipase A2 were found in Groups X and XIIA.

They concluded that there was an increased expression of secreted phospholipase A2-X and suggested that this may play a role in the dysregulated eicosanoid synthesis in asthma.

Reference
Hallstrand TS, et al. Secreted phospholipase A2 Group X Overexpression in Asthma and Bronchial Hyperresponsiveness. Am J Respir Crit Care Med 2007; 176:1072-1078.

 

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