Human epidermis transforms exogenous leukotriene A4 into peptide leukotrienes: possible role in transcellular metabolism.
Leukotriene B4 formation can take place by cell interaction between keratinocytes and neutrophils. Thus, keratinocytes without proven 5-lipoxygenase activity can transform neutrophil-derived leukotriene A4 into leukotriene B4. The purpose of the present study was to investigate whether human epidermis is able to transform leukotriene A4 sequentially into the peptide leukotrienes (LTC4, LTD4 and LTE4). Epidermis isolated using the suction blister technique or keratomed skin specimens were incubated with either neutrophils or exogenously added leukotriene A4. Peptide leukotrienes were determined by integrated optical density after RP-HPLC separation, and the identity of leukotrine C4 was confirmed by (1) the retention time similarity with authentic leukotriene C4; (2) the UV spectrum determined with an on-line diode array detector; and (3) conversion by gamma-glutamyl transpeptidase of the peak coeluting with authentic leukotriene C4 into a new peak coeluting with authentic leukotriene D4. The results of this study showed that while human epidermis cannot form detectable amounts of peptide leukotrienes by itself, it can transform exogenous leukotriene A4 into peptide leukotrienes. Furthermore, coincubation of human epidermis and neutrophils resulted in a marked increase (90%) in peptide leukotriene formation when compared with neutrophils alone, indicating that human epidermis can transform neutrophil-derived leukotriene A4 into peptide leukotrienes. These results indicate that human skin contains leukotriene C4 synthase activity capable of producing significant amounts of leukotriene C4 from leukotriene A4, and that the keratinocytes may play a more active role in peptide leukotriene formation in the skin than previously thought.(ABSTRACT TRUNCATED AT 250 WORDS)
Iversen
L
L
Department of Dermatology, Marselisborg Hospital, University of Aarhus, Denmark.
Kristensen
P
P
Grøn
B
B
Ziboh
V A
VA
Kragballe
K
K
D001711:Biotransformation; D002216:Captopril / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004817:Epidermis / Q000378:metabolism*; D004976:Ethacrynic Acid / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D017572:Leukotriene A4 / Q000493:pharmacokinetics*; D007975:Leukotriene B4 / Q000378:metabolism; D017997:Leukotriene C4 / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D017572:Leukotriene A4; D015289:Leukotrienes; D007975:Leukotriene B4; D017997:Leukotriene C4; D002216:Captopril; D009195:Peroxidase; D005723:gamma-Glutamyltransferase; D007930:Leucine; C012211:ubenimex; D004976:Ethacrynic Acid