An in vivo approach showing the chemotactic activity of leukotriene B-4 inacute renal ischemic-reperfusion injury

Neutrophil migration protects the body against foreign invasion. Sequestrat ion and activation of neutrophils, however, require stringent regulation be cause they may also cause tissue damage by the release of lysosomal enzymes and reactive oxygen species. The activity of various chemoattractants [e.g ., leukotriene B-4 (LTB4), interleukin-8, and complements] has been documen ted by in vitro assays, whereas in vivo data have been limited mostly to hi stology. To examine in an in vivo model the chemotactic activity and subseq uent tissue infiltration and the role of a specific chemoattractant, LTB4, we used a rat renal ischemia-reperfusion injury model. Fluorescence-labeled Chinese hamster ovary (CHO) cells stably expressing the LTB4 receptor (CHO -BLT) were able to accumulate along with neutrophils in the postischemic ki dney, in contrast to vector control CHO cells. Furthermore, LTB4 antagonist s that protect against the decrease in renal function and diminish the tiss ue myeloperoxidase activity also led to the marked decrease in the number o f CHO-BLT cells and neutrophils. Thus, LTB4 alone appears sufficient to cau se cells to migrate into postischemic tissues, and its dominant role in rep erfusion injury has been demonstrated. The utilization of transfectants to pinpoint the role of LTB4 in these in vivo experiments suggests their poten tial use with other ligands and/or in other pathological conditions.