Magainin-2 releases histamine from rat mast cells.
The magainins are basic 23 amino acid peptides with a broad spectrum of antimicrobial activity. Their bactericidal effect has been attributed to their capacity to interact with lipid bilayer membranes. We observed histamine release by magainin-2 amide from rat peritoneal mast cells (ED50 = 13 micrograms/ml) but not from human basophils. This histamine-releasing reaction from peritoneal mast cells was due to a secretory rather than cytolytic effect, i.e., release occurred without concomitant liberation of lactic dehydrogenase. Furthermore, the pretreatment of mast cells with magainin-2 amide did not desensitize cells against subsequent challenge with other secretagogues. Maximum histamine release occurred in less than a minute at 25 and 37 degrees C. The addition of Ca2+ was not required for histamine release, although release was enhanced by the addition of 0.3-1 mM Ca2+. The addition of 3 mM Ca2+ or Mg2+ was markedly inhibitory. The presence of Na+ or Cl- ions in the medium was not required for release. Therefore, histamine release is not due to the formation of anion-selective channels in the membrane of mast cells. The results indicated that the characteristics of histamine secretion induced by magainin-2 amide were unlike IgE-mediated release but were similar to the mechanism of release attributed to some other basic peptides and to compound 48/80.
Clinical Immunology Section, Laboratory of Immunology National Institute of Dental Research, Bethesda, Maryland 20892.
W A
WA
Hook
S
S
Tsuji
R P
RP
Siraganian
D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D002118:Calcium / Q000494:pharmacology; D002460:Cell Line; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015471:Leukemia, Basophilic, Acute; D054806:Magainins; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013696:Temperature; D029867:Xenopus Proteins
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D054806:Magainins; D010455:Peptides; D029867:Xenopus Proteins; C053301:magainin 2 peptide, Xenopus; D007770:L-Lactate Dehydrogenase; D008274:Magnesium; D002118:Calcium