Magainin-2 Releases Histamine from Rat Mast Cells

Abstract

Abstract

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 μg/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°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.