Calcium ionophore A23187 and compound 48/80 induce PGD2 and tryptase in human cord blood-derived mast cells: lack of effect of il-18

Immunological and biochemical reactions associated with inflammation are elicited in response to a physical or immunological challenge. Early in inflammation there is mobilization and infiltration of neutrophils, mast cells and macrophages to the site ofinflammation. These cells release pro-inflammatory compounds icluding cytokines, vasoactive peptides (eg., histamine), and eicosanoids. The release of prostaglandin D2 (PGD2) and tryptase induced by anti-IgE, A23187 and compound 48/80 were studied using in vitro a good and valid model of human cord blood-derived mast cells (HCBDMC). Tryptase is a mast cell product and enhances vasopermeability with anticoagulant activities. In this study we measure the release ofPGD2 and tryptase on mast cells activate by anti-IgE, calcium ionophoreA23187, polybasic compound 48/80 (an agent containing a cationic region adjacent to a hydrophobic moiety, which works by activating G proteins) and IL-18. The generation of PGD2 was measured by radioimmunoassay. Release of PGD2 was detectable (after 12 h) following challenge with anti-IgE, A23187 and compound 48/80. Our data show that mature HCBDMC produce proinflammatory PGD2 following triggering with anti-IgE and with IgE-independent agonists, such as calcium ionophoreA23187 and polybasic compound 48/80, while IL-18 was unable to stimulate the release of PGD2 or tryptase on HCBDMC. Although a great deal has been learned about the mediators produced by mast cells, the ultimate biologic function(s) of mast cells remains a mystery