ROLE OF LIPOXIN-A4 AND LIPOXIN-B4 IN THE GENERATION OF ARACHIDONIC-ACID METABOLITES BY RAT MAST-CELLS AND THEIR EFFECT ON [H-3] SEROTONIN RELEASE

Basophils located in tissues are called mast cells and are found in connective tissue. Many different compounds are secreted from basophil granules upon appropriate stimulation. Products such as heparin, histamine, serotonin (5-hydroxytryptamine, 5-HT), and membrane-derived materials which give rise to arachidonic acid metabolites, such as prostaglandins and leukotrienes, are some of the more important compounds released by mast cells. These compounds, when released after stimulation with a variety of molecules, such as IgE, specific antigen anaphylatoxin, as well as the compound 48/80 (C48/80) or calcium ionophore A23187, cause contraction of endothelial cells and mediate atopic or anaphylactic hypersensitivity. In this report, we study the generation of some arachidonic acid products, namely leukotrienes C4, D4, E4, and B4 and the prostaglandins D2 and E2 by rat peritoneal mast cells (RPMC), using calcium ionophore A23187 as a degranulating agonist. We have also studied the new lipoxygenase products, lipoxins A4 and B4, on RPMC secretion using C48/80 as a secretagogue. A rat basophilic leukemia cell line (RBL) was also used to compare results with RPMC. In this paper we have demonstrated that RPMC stimulated with A23187 release LTC4, LTD4, LTE4 and LTB4 and also PGD2 but not PGE2. These results were also confirmed when RBLs were used. In addition, we have shown that mast cells pretreated with LTC4, LTD4, LTE4 or 15-HETE do not modify the release of [H-3]5HT exerted by C48/80 (0.5-mu-g/ml) or A23187 (5-mu-g/ml). When LXA4 or B4 was used, mast cells were inhibited slightly (not statistically significant) from degranulating after the secretagogue treatment. However, when LXA4 or B4 was used at the highest concentration (1-mu-M) for 15 min, followed by the addition of the secretagogue for 10 min, a little but significant inhibition was found. In this report, we show that the generation of LTC4, D4 and E4 by mast cells certainly has no autocrine influence, since we found a non-significant effect of these lipoxygenase products on mast cell secretion. However, since LTB4 is generated by RPMC and other cells [11], it is possible that mast cells together with neutrophils participate in the increasing leukocyte adhesion to endothelium in small venules. We report for the first time the influence of LXA4 and B4 on mast cell secretion. The results are very inconsistent, however, evidencing a slight inhibitory potential of these two 15-HETE derivatives on mast cell secretion.