Leukotriene B4 and Thromboxane A2 are Essential Cofactors in CD 18 Dependent Neutrophil Diapedesis

摘要

This study tests the ability of thromboxane (Tx) to induce leukotriene B (LTB) sub 4 synthesis which then leads to activation of peripheral blood neutrophils (PMN) and endothelial adhesion receptors. Tx-mimic (U 46619, 1 micrograms/ml) was administered into abraded skin chambers placed on the back of rabbits (n=6). After 3 h, LTB sub 4 was synthesized in the blister fluid, 385 pg/ml, a value higher than levels in saline treated blisters 10 pg/ml (p<0.05). The LTB sub 4 generation following Tx-mimic was correlated (p<0.05, r=0.70) with neutrophil diapedesis. These averaged 645 PMN/cu mm, higher than saline values of 20 PMN/cu mm (p<0. 05). Intravenous (IV) treatment of other rabbits (n=4) with the lipoxygenase inhibitor diethylcarbamazine 60 mg/kg followed by 40 mg/kg/h prevented Tx-mimic induced LTB sub 4 synthesis (10 pg/ml) and diapedesis 19 PMN/cu mm(both p<0.05). IV treatment of yet other rabbits (n=4) with the anti-CD 18 monoclonal antibody R 15.7, 1 mg/kg abolished Tx-induced diapedesis (3 PMN/cu mm) (p<0. 05). In contrast, local administration of the protein synthesis inhibitor actinomycin D 3 ng, 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 LTB sub 4 and activation of neutrophil CD 18 but not endothelial adhesion receptors.