The metabolism "in vitro" of leukotriene B₄ in blood of normal subjects and asthmatic patients

Zakrzewski, J. T., Sampson, A. P., Evans, J. M., Barnes, N. C., Piper, P. J. and Castello, J. F. (1988) The metabolism "in vitro" of leukotriene B₄ in blood of normal subjects and asthmatic patients. Prostaglandins, 35 (6), 869-883. (doi:10.1016/0090-6980(88)90113-X).

Abstract

The metabolism of exogenous leukotriene B₄ (LTB₄) was investigated in venous blood obtained from normal and asthmatic subjects. Using specific radioimmunoassay (RIA) and reverse-phase high performance liquid chromatography (RP-HPLC) techniques we have demonstrated that LTB₄ is relatively stable during a 2 hr incubation period at 37°C in our system in vitro. Nevertheless, chromatographic analysis revealed the presence of two products which had retention times identical to 20-hydroxy LTB₄ (20-0H LTB₄) and 20-carboxy LTB₄ (20-C00H LTB₄) in which the dicarboxylic derivative was the main metabolite present after 15 min incubation. The amount of LTB₄ and its w-oxidation products observed after a 2 hr incubation period was 73% and 24% respectively. There was no basal release of LTB₄ from blood. The appearance of these oxidative products was totally suppressed at 4°C and with incubations performed with either venous plasma or Hartmann's control. No significant difference was observed in substrate metabolism between normal and asthmatic subjects. Our results demonstrate that LTB₄ is slowly degraded in human whole blood through a cellular dependent process of w-oxidation which may be an important pathway for regulating the availability of this potent biologically active substance.

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Contributors

Author: A. P. Sampson

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