title: Role of CX3CL1 in the chemotactic migration of all-trans retinoic acid-treated acute promyelocytic leukemic cells toward apoptotic cells.
abstract: BACKGROUND
  Phagocytic clearance of apoptotic neutrophils by tissue macrophages is a crucial component in the resolution phase of acute inflammation. However, the number of tissue macrophages is low and not likely to cope satisfactorily with the excess number of dying neutrophils. Although recent studies have reported that neutrophils are able to engulf apoptotic neutrophils, the mechanisms by which living neutrophils are attracted to apoptotic neutrophils are poorly defined. Increased amounts of CX3CL1 and microparticles (MPs) are rapidly released by apoptotic cells, and are involved in the chemoattraction of mononuclear phagocytes toward apoptotic cells. The current study investigated the role of CX3CL1 in the chemoattraction of all-trans retinoic acid (ATRA)-treated NB4 (ATRA-NB4) cells toward apoptotic cells.
  
  
  METHODS
  Conditioning medium and MPs were harvested from apoptotic ATRA-NB4 cell cultures to determine their effects on living ATRA-NB4 cells by transmigration assay and adhesion assay. The cytokine levels in the conditioning medium were determined by enzyme-linked immunosorbent assay. Expression of CX3CR1 (a receptor of CX3CL1) on ATRA-NB4 cells was determined by flow cytometric analysis.
  
  
  RESULTS
  ATRA-NB4 cells transmigrated toward the apoptotic ATRA-NB4 cells, and this chemoattraction was partially inhibited when the CX3CR1 on ATRA-NB4 cells was blocked by its specific antibody. Both exogenous CX3CL1 and MPs released by apoptotic ATRA-NB4 cells were able to enhance the chemoattraction of ATRA-NB4 cells toward apoptotic cells or the adhesion of ATRA-NB4 cells to endothelial cells. CX3CL1 was expressed on the surface of MPs, and blocking this CX3CL1 with its specific antibody was able to partially inhibit the chemoattractive property of MPs.
  
  
  CONCLUSIONS
  CX3CL1, in either the free or MP form, is released rapidly by apoptotic ATRA-NB4 cells after induction of apoptosis to mediate the chemoattraction of living ATRA-NB4 cells toward apoptotic cells.
authors.affiliation: Department of Respiratory Therapy, Taipei Medical University, Taipei, Taiwan, ROC.
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Tsai
authors.affiliation: Department of Respiratory Therapy, Taipei Medical University, Taipei, Taiwan, ROC.
authors.forename: Chung-Hung
authors.initials: CH
authors.lastname: Shih
authors.affiliation: Department of Physiology, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Shan-Yu
authors.initials: SY
authors.lastname: Feng
authors.affiliation: Department of Physiology, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Shao-Chi
authors.initials: SC
authors.lastname: Chang
authors.affiliation: Department of Physiology, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Department of Physiology, National Yang-Ming University, Taipei, Taiwan, ROC; Department of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. Electronic address: hchsu@vghtpe.gov.tw.
authors.forename: Hui-Chi
authors.initials: HC
authors.lastname: Hsu
mesh_terms: D017209:Apoptosis; D002478:Cells, Cultured; D054428:Chemokine CX3CL1 / Q000502:physiology*; D002633:Chemotaxis / Q000502:physiology*; D005434:Flow Cytometry; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D009504:Neutrophils / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D014212:Tretinoin
keywords: CX3CL1; acute promyelocytic leukemia; apoptosis; chemotaxis; microparticles