Thromboxane A2 induces leukotriene B4 synthesis that in turn mediates neutrophil diapedesis via CD 18 activation

Gideon Goldman, Richard Welbourn, C. Robert Valeri, David Shepro, Herbert B. Hechtman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Previous studies have indicated that thromboxane (Tx) and leukotriene (LT) B4 act synergistically to induce neutrophil (PMN) adhesion in the microvasculature. This study explores the ability of Tx to induce LTB4 synthesis, which then leads to activation of PMN and endothelial adhesion receptors. Tx-mimic (U46619, 1 μg/ml) was administered into abraded skin chambers placed on the backs of rabbits (n = 6). After 3 hr LTB4 was synthesized in the blister fluid at 385 pg/ml, a value higher than levels in saline-treated blisters, 10 pg/ml (P < 0.05). The LTB4 generation following Tx-mimic was correlated (P < 0.05, r = 0.70) with neutrophil diapedesis. These averaged 645 PMN/mm3, values higher than saline values of 20 PMN/mm3 (P < 0.05). Intravenous (iv) treatment of other rabbits (n = 4) with the lipoxygenase inhibitor diethylcarbamazine at 60 mg/kg, followed by 40 mg/kg/hr, prevented Tx-mimic-induced LTB4 synthesis (10 pg/ml) and diapedesis (19 PMN/mm3) (both P < 0.05). Intravenous treatment of yet other rabbits (n = 4) with the anti-CD 18 monoclonal antibody R 15.7 at 1 mg/kg abolished Tx-induced diapedesis (3 PMN/mm3) (P < 0.05). In contrast, local administration of 3 ng of the protein synthesis inhibitor actinomycin D, to prevent expression of endothelial adhesion proteins, limited TNF- but not Tx-induced diapedesis. The data indicate that Tx-induced diapedesis is mediated by the generation of LTB4 and the activation of neutrophil CD 18 but not endothelial adhesion proteins.

Original languageEnglish
Pages (from-to)367-375
Number of pages9
JournalMicrovascular Research
Issue number3
StatePublished - May 1991
Externally publishedYes


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