Open AccessAn in vivo approach showing the chemotactic activity of leukotriene B 4 in acute renal ischemic-reperfusion injury
Author(s) -
Eisei Noiri,
Takehiko Yokomizo,
Akihide Nakao,
Tohru Izumi,
Toshiro Fujita,
Satoshi Kimura,
Takao Shimizu
Publication year - 2000
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.97.2.823
Subject(s) - in vivo , chemotaxis , chinese hamster ovary cell , leukotriene b4 , myeloperoxidase , kidney , reperfusion injury , leukotriene , inflammation , chemistry , biology , ischemia , microbiology and biotechnology , receptor , immunology , medicine , endocrinology , biochemistry , asthma
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.g., leukotriene B4 (LTB4 ), interleukin-8, and complements] has been documented byin vitro assays, whereasin vivo data have been limited mostly to histology. To examine in anin vivo model the chemotactic activity and subsequent 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 kidney, in contrast to vector control CHO cells. Furthermore, LTB4 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, LTB4 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 LTB4 in thesein vivo experiments suggests their potential use with other ligands and/or in other pathological conditions.