Metabolism of leukotriene C4, D4 and E4 in allergic inflammation in rats

Using an allergic inflammation model of air pouch type in rats, levels of peptide-leukotriene (LT) C4, D4 and E4 in the pouch fluid were measured chromatographically, and peptide-LT metabolizing activities in the pouch fluid in the anaphylactic phase were examined. 10 min after injection of an antigen (azobenzene arsonate-conjugated acetyl bovine serum albumin) solution into a preformed air pouch on the back of the immunized rats, LTC4 level in the pouch fluid was the highest, followed by LTD4 and LTE4. At 30 min, the order of the level was reversed to LTE4 greater than LTD4 greater than LTC4, and total amount of peptide-LTs (LTC4 + LTD4 + LTE4) was the highest. Supernatant fraction of the pouch fluid collected 30 min after the antigenic challenge, converted [3H]LTC4 into [3H]LTD4, and [3H]LTD4 into [3H]LTE4 in time- and concentration-dependent manner. [3H]LTE4 was not metabolized under these conditions. Heat denaturation of the pouch fluid diminished the conversion of [3H]LTC4 into [3H]LTD4, and [3H]LTD4 into [3H]LTE4. In the granule fraction of purified mast cells, no metabolic activity of [3H]LTs was found. In intact mast cells as well as degranulating mast cells, a small but significant amount of [3H]LTC4 was metabolized into [3H]LTD4 and [3H]LTE4. In contrast, rat serum showed potent metabolizing activities of peptide-LTs. Since plasma exudation into the pouch is very prominent in the anaphylactic phase in this model, peptide-LT metabolizing activities in the pouch fluid are suggested to be attributable to plasma leaked into the pouch during the anaphylactic phase.