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 performed 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 > LTF₄ > LTC₄, and total amount of peptide-LTs (LTC₄ + LTD₄ + LTD₄) 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.