Inhibition of histamine release from human mast cells by natural chymase inhibitors

Acta Pharmacol Sin. 2004 Jun;25(6):822-6.

Abstract

Aim: To investigate the ability of natural chymase inhibitors to modulate histamine release from human mast cells.

Methods: Enzymatically dispersed cells from human lung, tonsil, and skin were challenged with anti-IgE or calcium ionophore A23187 in the absence or presence of the natural chymase inhibitors secretory leukocyte protease inhibitor (SLPI) and alpha(1)-antitrypsin, then histamine release was determined.

Results: IgE-dependent histamine release from lung, tonsil, and skin mast cells were inhibited by up to 70 %, 61 %, and 62 %, respectively following incubation with alpha(1)-antitrypsin (5000 nmol/L). SLPI 5000 nmol/L was also able to inhibit anti-IgE-dependent histamine released from lung, tonsil and skin mast cells by up to approximately 72 %, 67 %, and 58 %, respectively. While neither alpha(1)-antitrypsin nor SLPI by themselves altered histamine release from lung, tonsil and skin mast cells, they were able to inhibit calcium ionophore-induced histamine release from lung and tonsil mast cells.

Conclusion: Both micro(1)-antitrypsin and SLPI could potently inhibit IgE-dependent and calcium ionophore- induced histamine release from dispersed human lung, tonsil, and skin mast cells in a concentration-dependent manner, which suggested that they were likely to play a protective role in mast cell associated diseases including allergy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Anti-Idiotypic / pharmacology
  • Calcimycin / pharmacology
  • Chymases
  • Histamine Release / drug effects*
  • Humans
  • Ionophores / pharmacology
  • Lung / cytology
  • Mast Cells / metabolism*
  • Palatine Tonsil / cytology
  • Proteinase Inhibitory Proteins, Secretory
  • Proteins / pharmacology*
  • Secretory Leukocyte Peptidase Inhibitor
  • Serine Endopeptidases / pharmacology
  • Serine Proteinase Inhibitors / pharmacology
  • Skin / cytology
  • alpha 1-Antitrypsin / pharmacology*

Substances

  • Antibodies, Anti-Idiotypic
  • Ionophores
  • Proteinase Inhibitory Proteins, Secretory
  • Proteins
  • SLPI protein, human
  • Secretory Leukocyte Peptidase Inhibitor
  • Serine Proteinase Inhibitors
  • alpha 1-Antitrypsin
  • anti-IgE antibodies
  • Calcimycin
  • Serine Endopeptidases
  • Chymases