An in vivo approach showing the chemotactic activity of leukotriene B4 in acute renal ischemic-reperfusion injury

摘要

Neutrophil migration protects the body against foreign invasion. Sequestration and activation of neutrophils. however, require stringent regulation because they may also cause tissue damage by the release of lysosomal enzymes and reactive oxygen species. The activity of various chemoattractants [e.9., leukotriene B4 (LTB4), interleukin-8, and complements] has been documented by in vitrO assays, whereas in vivo data have been limited mostly to histology. To examine in an in vivo model the chemotactic activity and Subsequent tissue infiltration and the role of a specific chemoat- tractant, LTB~4, we used a rat renal ischemia-reperfusion injury model. Fluorescence-labeled Chinese hamster ovary (CHO) cells stably expressing the LTB~4 receptor (CHO-BLT) were able to accu- mulate along with neutrophils in the postischemic kidney, in contrast to vector control CHO cells. Furthermore, LTB~4 antagonists that protect against the decrease in renal function and diminish the tissue myeloperoxidase activity also led to the marked decrease in the number of CHO-BLT cells and neutrophils. Thus, LTB~4 alone appears sufficient to cause cells to migrate into postischemic tissues, and its dominant role in reperfusion injury has been demonstrated. The utilization of transfectants to pinpoint the role of LTB' in these in vivo experiments suggests their potential use with other ligands and/or in other pathological conditions.