CROMOLYN INHIBITION OF MEDIATOR RELEASE IN MAST-CELLS DERIVED FROM MOUSE BONE-MARROW

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Abstract
Mast cells derived from mouse bone marrow fail to demonstrate a disodium-cromoglycate-induced inhibition of mediator release when the cromolyn is added simultaneously with a secretagogue. To investigate the long-term effects of cromolyn exposure, cells from BALB/C femoral bone marrow stimulated with IL-3 were cultured in the presence of 1 to 100 .mu.M cromolyn and demonstrated a similar viability and ability to proliferate as cells cultured in medium alone. Those cultured in cromolyn exhibited a significantly decreased A23187-or antigen-induced release of .beta.-hexosaminidase (4.3 .+-. 0.7% versus 9.2 .+-. 1.0%, p < 0.01) compared with control cells. The adenosine-induced potentiation of mediator release was diminished to a comparable degree after cromolyn exposure in culture. This inhibition was dose-dependent between 1 and 100 .mu.M cromolyn, evident by 5 days, reversible in 6 more days, and applied to immunoreactive leukotriene C4 generation as well. Bone marrow mast cells respond to chronic cromolyn exposure with a global inhibition of mediator release, but the basis for this response is unknown.