Evaluation of the effects of peptide antibiotics human beta-defensins-1/-2 and LL-37 on histamine release and prostaglandin D(2) production from mast cells

Eur J Immunol. 2001 Apr;31(4):1066-75. doi: 10.1002/1521-4141(200104)31:4<1066::aid-immu1066>3.0.co;2-#.

Abstract

Antimicrobial peptides, human beta-defensins (hBD-1/-2), and LL-37 (a peptide of human cathelicidin CAP18) are predominately expressed at epithelial tissues, where they participate in the innate host defense by killing invading microorganisms. In this study, to investigate the interactions between epithelial cell-derived antimicrobial peptides and mast cells, we evaluated the effects of hBD-1/-2 and LL-37 on mast cell functions using rat peritoneal mast cells. hBD-2 and LL-37 but not hBD-1 induced histamine release and intracellular Ca(2+) mobilization, and hBD-2 was more potent than LL-37. Interestingly, histamine release and intracellular Ca(2+) mobilization elicited by hBD-2 and LL-37 were markedly suppressed by BAPTA-AM (an intracellular Ca(2+) chelating agent), pertussis toxin and U-73122 (a phospholipase C inhibitor). In addition, among the peptides examined, only hBD-2 significantly induced PGD(2) production, which was abolished by indomethacin (cyclooxygenase-1/-2 inhibitor) but not NS-398 (cyclooxygenase-2 inhibitor), suggesting that hBD-2-induced PGD(2) production is mediated by cyclooxygenase-1. Likewise, the PGD(2) production was suppressed by pertussis toxin and U-73122. These observations suggest that hBD-2 and LL-37 stimulate mast cells to mobilize intracellular Ca(2+) and release histamine or generate PGD(2) in a G protein-phospholipase C-dependent manner. Thus, hBD-2 and LL-37 may have modulatory effects on inflammatory reactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Antimicrobial Cationic Peptides*
  • Arachidonic Acid / metabolism
  • Calcium / metabolism
  • Calcium / pharmacology
  • Calcium Signaling / drug effects
  • Carrier Proteins / pharmacology*
  • Cathelicidins
  • Chelating Agents / pharmacology
  • Cyclooxygenase Inhibitors / pharmacology
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Estrenes / pharmacology
  • Histamine / metabolism*
  • Humans
  • Magnesium / pharmacology
  • Male
  • Mast Cells / drug effects*
  • Mast Cells / enzymology
  • Mast Cells / metabolism
  • Molecular Sequence Data
  • Pertussis Toxin
  • Prostaglandin D2 / biosynthesis*
  • Pyrrolidinones / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Type C Phospholipases / antagonists & inhibitors
  • Type C Phospholipases / metabolism
  • Virulence Factors, Bordetella / pharmacology
  • beta-Defensins / chemistry
  • beta-Defensins / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Carrier Proteins
  • Cathelicidins
  • Chelating Agents
  • Cyclooxygenase Inhibitors
  • Estrenes
  • Pyrrolidinones
  • Virulence Factors, Bordetella
  • beta-Defensins
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
  • Arachidonic Acid
  • ropocamptide
  • Egtazic Acid
  • Histamine
  • Pertussis Toxin
  • Type C Phospholipases
  • Magnesium
  • Prostaglandin D2
  • Calcium