Correlation between mouse skin inflammation induced by arachidonic acid and eicosanoid synthesis.
We and others have shown that arachidonic acid (AA), when applied topically to ear surfaces, causes an intense acute inflammatory reaction within minutes (as measured by ear thickness). In this study, we have investigated the cellular and biochemical changes associated with this phenomenon and have attempted to correlate these changes with the induction of inflammation. Measurement of vascular permeability by the accumulation of [125I]albumin showed that significant plasma exudation was observed at 15 min in AA-treated ears. Furthermore, the increase in [125I]albumin was time related and was nearly 10-fold greater than control at 1 h. No time-related change in plasma exudation was observed with control ears. Measurement of LTC4 by radioimmunoassay showed that there was a significant increase in LTC4 synthesis at 15 min after AA treatment. Maximal LTC4 synthesis occurred at 15 min and subsequently decreased to 30% of peak level at 30 min. Histological examination and myeloperoxidase measurement indicated that few neutrophils were present at these early time points and suggested that cells other than neutrophils are contributing to LTC4 synthesis. Ear thickness, [125I]albumin accumulation and leukotriene C4 (LTC4) synthesis in AA-treated ears were reduced significantly by topically administered mixed lipoxygenase (LO) and cyclooxygenase inhibitors such as BW755C and phenidone. Therefore, we suggest that AA-induced ear inflammation is a suitable screen for detecting LO inhibitors in vivo.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000633:toxicity*; D002199:Capillary Permeability / Q000187:drug effects; D003877:Dermatitis, Contact / Q000209:etiology*; D015232:Dinoprostone; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008775:Methylprednisolone / Q000494:pharmacology; D051379:Mice; D011458:Prostaglandins E / Q000096:biosynthesis*; D011720:Pyrazoles / Q000494:pharmacology; D013189:SRS-A / Q000096:biosynthesis*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism
D001095:Arachidonic Acids; D011458:Prostaglandins E; D011720:Pyrazoles; D013189:SRS-A; D016718:Arachidonic Acid; C015429:phenidone; D015232:Dinoprostone; D008775:Methylprednisolone; D007213:Indomethacin