Effects of antibacterial peptides on mast cell functions

Abstract

Antimicrobial peptides, defensins (human β-defensins, hBDs-1/-2) and LL-37 (a peptide of human cathelicidin CAP 18) are expressed at epithelial tissues, where they participate in the innate host defense by killing invaded microorganisms. We have evaluated the effects of hBD-1/-2 and LL-37 on mast cell functions (histamine release and PGD2 production) using rat peritoneal mast cells. The results revealed that hBD-2 and LL-37 but not hBD-1 induced histamine release and intracellular Ca2+ mobilization, and that hBD-2 was more potent than LL-37. Interestingly, histamine release and intracellular Ca2+ mobilization elicited by hBD-2 and LL-37 were markedly suppressed by both pertussis toxin (PTx) and U-73122, a phospholipase C (PLC) inhibitor. In addition, among the peptides examined, only hBD-2 induced PGD2 production that was completely abolished by indomethacin (COX-1/-2 inhibitor) but not NS-398 (COX-2 inhibitor), suggesting that hBD-2-induced PGD2 production is mediated by COX-1 but not COX-2. Likewise, the PGD2 production was completely suppressed by PTx and U-73122. We suggest that hBD-2 and LL-37 activate mast cells to mobilize intracellular Ca2+ and release histamine or generate PGD2 in a G protein-PLC-dependent manner. Thus, hBD-2 and LL-37 may have modulatory effects on inflammatory and allergic reactions by releasing histamine and/or prostanoids from mast cells.