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P-Selectin and P-Selectin Glycoprotein Ligand 1 Mediate Rolling of Activated CD8+ T Cells in Inflamed Colonic Venules
  1. Muhammad Asaduzzaman, PhD*,
  2. Andrada Mihaescu, MD*,
  3. Yusheng Wang, PhD*,
  4. Tohru Sato, MD,
  5. Henrik Thorlacius, MD, PhD*
  1. From the *Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden; and †Department of Medicine, Stanford University School of Medicine, Stanford, CA.
  1. Received April 26, 2009, and in revised form June 9, 2009.
  2. Accepted for publication July 3, 2009.
  3. Reprints: Henrik Thorlacius, MD, PhD, Department of Surgery, Malmo¨ University Hospital, Lund University, 205 02 Malmö, Sweden. E-mail: henrik.thorlacius{at}
  4. This work was supported by grants from the Swedish Medical Research Council, Crafoordska stiftelsen, Blanceflors stiftelse, Einar och Inga Nilssons stiftelse, Harald och Greta Jaenssons stiftelse, Greta och Johan Kocks stiftelser, Fröken Agnes Nilssons stiftelse, Franke och Margareta Bergqvists stiftelse för främjande av cancerforskning, Magnus Bergvalls stiftelse, Mossfelts stiftelse, Nanna Svartz stiftelse, Ruth och Richard Julins stiftelse, Svenska Läkaresällskapet, Teggers stiftelse, Allmäna sjukhusets i Malmö stiftelse för bekämpande av cancer, MAS fonder, Malmö University Hospital, and Lund University.


Background Activated T cells regulate inflammatory diseases in the intestinal tract; however, the adhesive mechanisms governing CD8+ T-cell recruitment in the colon are not known.

Methods Herein, we used a graft-versus-host disease (GvHD) model to study CD8+ T-cell rolling and adhesion in the large intestine by use of intravital fluorescence microscopy. Graft-versus-host disease was induced by transferring 50 × 106 allogeneic donor splenocytes from BDF1, B6, H-2b mice to recipient BDF1, H-2bxd mice. After 8 days, rhodamine-labeled CD8+ T cells (4 × 106) from healthy and GvHD mice were injected into both healthy and GvHD recipient mice, and CD8+ T-cell-endothelium interactions were studied in the colon.

Results Activated CD8+ T cells from GvHD mice expressed higher levels of P-selectin ligand and decreased levels of L-selectin. Immunoneutralization of P-selectin and P-selectin glycoprotein ligand 1 reduced CD8+ T-cell rolling and adhesion in inflamed colonic venules by more than 71%. Inhibition of E-selectin had no effect on GvHD-induced CD8+ T-cell-endothelium interactions.

Conclusions We conclude that P-selectin and P-selectin glycoprotein ligand 1 are dominating molecules in supporting adhesive interactions of CD8+ T cells in inflamed colonic venules and may be useful targets to protect against pathological inflammation in the large bowel.

Key Words
  • adhesion
  • colon
  • inflammation
  • lymphocyte
  • rolling

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