Platelet activating factor does not release histamine from human dispersed cutaneous mast cells

Area of Science:

• Immunology
• Dermatology
• Pharmacology

Background:

• Histamine H1-antagonists reduce weal-and-flare responses to platelet-activating factor (PAF) in human skin, suggesting mast cell histamine release is involved.
• The precise mechanism of PAF-induced histamine release from cutaneous mast cells requires further investigation.

Purpose of the Study:

• To investigate the interaction of PAF with human cutaneous mast cells.
• To determine if PAF directly releases histamine, potentiates other mast cell stimulants, or induces histamine-releasing factors (HRFs).

Main Methods:

• Human dispersed foreskin mast cells were incubated with PAF (C18 and C16) at various concentrations.
• Histamine release was measured, and experiments were conducted with and without extracellular calcium, metabolic energy, and in the presence of PAF antagonists (WEB 2086, BN 52021).
• PAF was also tested for its ability to potentiate anti-IgE, A23187, or substance P, and to induce HRFs from platelets and leucocytes.

Main Results:

• High concentrations of PAF (100 microM) induced significant histamine release (83.5-88.2%) from mast cells, indicating a cytotoxic mechanism.
• This high-concentration histamine release was independent of extracellular calcium, metabolic energy, and specific PAF antagonists.
• Lower PAF concentrations (10 nM-1 microM) did not potentiate mast cell stimulants or induce HRFs from leukocytes and platelets.

Conclusions:

• Platelet-activating factor (PAF) at high concentrations (100 microM) directly induces histamine release from human cutaneous mast cells via a cytotoxic mechanism.
• PAF at lower concentrations does not appear to act indirectly by potentiating other mast cell stimulants or by releasing histamine-releasing factors from leukocytes and platelets.