New role for heparan sulfate: regulator of leukotriene generation in mouse E-mast cells

In this work, bovine heparan sulfate, pig mucosa heparin and squid chondroitin sulfate-E glycosaminoglycans (GAGs) were compared as to their affect on the synthesis of leukotrienes C4 (LTC4) and B4 (LTB4) as well as on the production of prostaglandin D2 (PGD2) in cultured mouse E-mast cells (E-MC). The maximum percent increase in LTC4 generation in cells treated with 0.2 micrograms heparan sulfate was 52 +/- 3% (mean +/- S.E., n = 5). Whereas 0.5 micrograms of the GAG increased the production of LTB4 by 50% Ten micrograms of heparin slightly increased the LTC4 production (33%) whereas lower doses were found to be ineffective. No significant increase in LTC4 production was demonstrated when the IgE sensitized E-MC were treated with chondroitin sulfate-E GAG prior to the antigen challenge. Neither one of the three GAGs, at the various doses used, affected the antigen induced exocytosis of beta-hexosaminidase from the IgE sensitized E-MC. After 15 min preincubation with heparan sulfate, antigen induced release of PGD2 from 1 X 10(6) sensitized cells was inhibited from 5.4 ng +/- 0.1 ng into 3.5 ng +/- 0.1 ng at 0.5 micrograms/ml GAG. All of the three types of GAGs used were uneffective when the E-MC were activated by calcium ionophore A23187.