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Endocytosis of Red Blood Cell Microparticles by Pulmonary Endothelial Cells is Mediated By Rab5.

Publication ,  Journal Article
Kim, Y; Abplanalp, WA; Jung, AD; Schuster, RM; Lentsch, AB; Gulbins, E; Caldwell, CC; Pritts, TA
Published in: Shock
March 2018

Microparticles are submicron vesicles shed from aging erythrocytes as a characteristic feature of the red blood cell (RBC) storage lesion. Exposure of pulmonary endothelial cells to RBC-derived microparticles promotes an inflammatory response, but the mechanisms underlying microparticle-induced endothelial cell activation are poorly understood. In the present study, cultured murine lung endothelial cells (MLECs) were treated with microparticles isolated from aged murine packed RBCs or vehicle. Microparticle-treated cells demonstrated increased expression of the adhesion molecules ICAM and E-selectin, as well as the cytokine, IL-6. To identify mechanisms that mediate these effects of microparticles on MLECs, cells were treated with microparticles covalently bound to carboxyfluorescein succinimidyl ester (CFSE) and cellular uptake of microparticles was quantified via flow cytometry. Compared with controls, there was a greater proportion of CFSE-positive MLECs from 15 min up to 24 h, suggesting endocytosis of the microparticles by endothelial cells. Colocalization of microparticles with lysosomes was observed via immunofluorescence, indicating endocytosis and endolysosomal trafficking. This process was inhibited by endocytosis inhibitors. SiRNA knockdown of Rab5 signaling protein in endothelial cells resulted in impaired microparticle uptake as compared with nonsense siRNA-treated cells, as well as an attenuation of the inflammatory response to microparticle treatment. Taken together, these data suggest that endocytosis of RBC-derived microparticles by lung endothelial cells results in endothelial cell activation. This response seems to be mediated, in part, by the Rab5 signaling protein.

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Published In

Shock

DOI

EISSN

1540-0514

Publication Date

March 2018

Volume

49

Issue

3

Start / End Page

288 / 294

Location

United States

Related Subject Headings

  • rab5 GTP-Binding Proteins
  • Respiratory Mucosa
  • Mice
  • Male
  • Lung
  • Erythrocytes
  • Epithelial Cells
  • Endocytosis
  • Emergency & Critical Care Medicine
  • Cell-Derived Microparticles
 

Citation

APA
Chicago
ICMJE
MLA
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Kim, Y., Abplanalp, W. A., Jung, A. D., Schuster, R. M., Lentsch, A. B., Gulbins, E., … Pritts, T. A. (2018). Endocytosis of Red Blood Cell Microparticles by Pulmonary Endothelial Cells is Mediated By Rab5. Shock, 49(3), 288–294. https://doi.org/10.1097/SHK.0000000000000995
Kim, Young, William A. Abplanalp, Andrew D. Jung, Rebecca M. Schuster, Alex B. Lentsch, Erich Gulbins, Charles C. Caldwell, and Timothy A. Pritts. “Endocytosis of Red Blood Cell Microparticles by Pulmonary Endothelial Cells is Mediated By Rab5.Shock 49, no. 3 (March 2018): 288–94. https://doi.org/10.1097/SHK.0000000000000995.
Kim Y, Abplanalp WA, Jung AD, Schuster RM, Lentsch AB, Gulbins E, et al. Endocytosis of Red Blood Cell Microparticles by Pulmonary Endothelial Cells is Mediated By Rab5. Shock. 2018 Mar;49(3):288–94.
Kim, Young, et al. “Endocytosis of Red Blood Cell Microparticles by Pulmonary Endothelial Cells is Mediated By Rab5.Shock, vol. 49, no. 3, Mar. 2018, pp. 288–94. Pubmed, doi:10.1097/SHK.0000000000000995.
Kim Y, Abplanalp WA, Jung AD, Schuster RM, Lentsch AB, Gulbins E, Caldwell CC, Pritts TA. Endocytosis of Red Blood Cell Microparticles by Pulmonary Endothelial Cells is Mediated By Rab5. Shock. 2018 Mar;49(3):288–294.

Published In

Shock

DOI

EISSN

1540-0514

Publication Date

March 2018

Volume

49

Issue

3

Start / End Page

288 / 294

Location

United States

Related Subject Headings

  • rab5 GTP-Binding Proteins
  • Respiratory Mucosa
  • Mice
  • Male
  • Lung
  • Erythrocytes
  • Epithelial Cells
  • Endocytosis
  • Emergency & Critical Care Medicine
  • Cell-Derived Microparticles