Mast cell tryptase may play a protective role in early inflammation in human small airway epithelial cells

Abstract

Small airway epithelial cells are the primary line of defense against inhaled environmental pathogens. Mast cell numbers are increased in asthmatic airways and release of mast cell mediators may regulate early inflammation. This study investigated the activation of calcium-independent phospholipase A2 (iPLA2) in response to tryptase stimulation of human small airways epithelial cells (HSAEC). Our results demonstrate that by 10 minutes tryptase stimulation lead to an increase in iPLA2 activity (2.5 ± 0.2 to 4.8 ± 0.18 nmol/mg protein/min, p<0.01, n=6)) and a subsequent increase in the release of arachidonic acid (0.6 ± 0.1 to 4.0 ± 0.1 %, p<0.01, n=6) and prostaglandin E2 (PGE2) (2107 ± 58 to 5344 ± 48 pg/mg protein, p<0.01, n=6). The increased iPLA2 activity was completely inhibited by pretreating the cells with bromoenol lactone (BEL, a selective iPLA2 inhibitor). BEL also inhibited the tryptase-induced arachidonic acid and PGE2 release from HSAEC. Previous studies have demonstrated that PGE2 can be beneficial in endothelial repair and thus our data suggest a protective action for mast cell degranulation. This work was supported by AHA Heartland Affiliate Grant# 0610118Z.