CX3CL1(+) microparticles mediate the chemoattraction of alveolar macrophages toward apoptotic acute promyelocytic leukemic cells

Cell Physiol Biochem. 2014;33(3):594-604. doi: 10.1159/000358637. Epub 2014 Feb 27.

Abstract

Background/aims: During the resolution phase of inflammation, release of "find-me" signals by apoptotic cells is crucial in the chemoattraction of macrophages toward apoptotic cells for subsequent phagocytosis, in which microparticles derived from apoptotic cells (apo-MPs) are involved. A recent study reports that CX3CL1 is released from apoptotic cells to stimulate macrophages chemotaxis. In this study, we investigated the role of CX3CL1 in the apo-MPs in the cell-cell interaction between alveolar macrophage NR8383 cells and apoptotic all-trans retinoic acid-treated NB4 (ATRA-NB4) cells.

Methods/results: Apoptotic ATRA-NB4 cells and their conditioning medium (CM) enhanced the chemoattraction of NR8383 cells as well as their phagocytosis activity in engulfing apoptotic ATRA-NB4 cells. The levels of CX3CL1(+) apo-MPs and CX3CL1 were rapidly elevated in the CM of ATRA-NB4 cell culture after induction of apoptosis. Both exogenous CX3CL1 and apo-MPs enhanced the transmigration of NR8383 cells toward apoptotic ATRA-NB4 cells. This pro-transmigratory activity was able to be partially inhibited either by blocking the CX3CR1 (CX3CL1 receptor) of NR8383 cells with its specific antibody or by blocking the surface CX3CL1 of apo-MPs with its specific antibody before incubating these apo-MPs with NR8383 cells.

Conclusion: CX3CL1(+) apo-MPs released by apoptotic cells mediate the chemotactic transmigration of alveolar macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Line, Tumor
  • Cell-Derived Microparticles / metabolism*
  • Cell-Derived Microparticles / pathology
  • Chemokine CX3CL1 / metabolism*
  • Chemotaxis*
  • Humans
  • Leukemia, Promyelocytic, Acute / metabolism*
  • Leukemia, Promyelocytic, Acute / pathology
  • Macrophages, Alveolar / metabolism*
  • Macrophages, Alveolar / pathology
  • Neoplasm Proteins / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Tretinoin / pharmacology

Substances

  • CX3CL1 protein, human
  • Chemokine CX3CL1
  • Cx3cl1 protein, rat
  • Neoplasm Proteins
  • Tretinoin