Kidney injury molecule-1 is a phosphatidylserine receptor that confers a phagocytic phenotype on epithelial cells.
Following injury, the clearance of apoptotic and necrotic cells is necessary for mitigation and resolution of inflammation and tissue repair. In addition to macrophages, which are traditionally assigned to this task, neighboring epithelial cells in the affected tissue are postulated to contribute to this process. Kidney injury molecule-1 (KIM-1 or TIM-1) is an immunoglobulin superfamily cell-surface protein not expressed by cells of the myeloid lineage but highly upregulated on the surface of injured kidney epithelial cells. Here we demonstrate that injured kidney epithelial cells assumed attributes of endogenous phagocytes. Confocal images confirm internalization of apoptotic bodies within KIM-1-expressing epithelial cells after injury in rat kidney tubules in vivo. KIM-1 was directly responsible for phagocytosis in cultured primary rat tubule epithelial cells and also porcine and canine epithelial cell lines. KIM-1 was able to specifically recognize apoptotic cell surface-specific epitopes phosphatidylserine, and oxidized lipoproteins, expressed by apoptotic tubular epithelial cells. Thus, KIM-1 is the first nonmyeloid phosphatidylserine receptor identified to our knowledge that transforms epithelial cells into semiprofessional phagocytes.
Ichimura
Takaharu
T
Renal Division, Brigham and Women's Hospital, Harvard Institutes of Medicine, Room 550, 4 Blackfan Circle, Boston, Massachusetts 02115, USA. tichimura@partners.org
Asseldonk
Edwin J P V
EJ
Humphreys
Benjamin D
BD
Gunaratnam
Lakshman
L
Duffield
Jeremy S
JS
Bonventre
Joseph V
JV
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010587:Phagocytosis / Q000502:physiology*; D010641:Phenotype; D010718:Phosphatidylserines / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D013552:Swine
D015815:Cell Adhesion Molecules; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D010718:Phosphatidylserines; D011956:Receptors, Cell Surface; C110936:Havcr1 protein, rat; C099252:oxidized low density lipoprotein; C408123:phosphatidylserine receptor