Leukotriene B4 and Thromboxane A2 are Essential Cofactors in CD 18 Dependent Neutrophil Diapedesis.
Abstract
Previous studies have indicated that thromboxane (Tx) and leukotriene (LT) B sub 4 act synergistically to induce neutrophil (PMN) adhesion in the microvasculature. This study tests the ability of Tx to induce LTB sub 4 synthesis which then leads to activation of 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/mm(exp 3), higher than saline values of 20 PMN/mm(exp 3) (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/mm(exp 3) (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/mm(exp 3)) (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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 25, 1990
- Accession Number
- ADA360180
Entities
People
- C. R. Aleri
- David Shepro
- Gideon Goldman
- Herbert B. Hechtman
- Richard Welbourn
Organizations
- Boston University