Platelet recruitment in the murine hepatic microvasculature during experimental sepsis: role of neutrophils

Microcirculation. 2006 Mar;13(2):89-97. doi: 10.1080/10739680500466343.

Abstract

Objectives: Sepsis is a major clinical problem that often results in the dysfunction or failure of multiple organs, including the liver. While inflammatory cell activation has been implicated as an early critical event in sepsis-induced liver dysfunction, there is growing evidence for the involvement of activated platelets in this pathologic process.

Methods: Intravital microscopy was used in this study to assess the magnitude and time course of platelet adhesion in the liver microcirculation during experimental sepsis and to determine whether the platelet accumulation is linked to leukocyte infiltration. The adhesion of platelets and leukocytes in terminal hepatic venules (THV) and sinusoids was quantified at 2, 4, and 6 h after abdominal sepsis induced by cecal ligation and puncture (CLP).

Results: While the rolling and firm adhesion of platelets and leukocytes in THV were not altered in the first 2 h after CLP, platelet recruitment was observed at 4 h and further elevated at 6 h after CLP. Leukocyte adhesion in THV exhibited a similar time course. A similar accumulation of blood cells in sinusoids was noted after CLP. This was accompanied by an increased number of nonperfused sinusoids. CLP-induced leukocyte and platelet recruitment in THV and sinusoids was attenuated in mice rendered neutropenic with anti-neutrophil serum.

Conclusion: These findings indicate that sepsis is associated with a neutrophil-dependent recruitment of platelets in the liver microcirculation that impairs sinusoidal perfusion and may contribute to the liver dysfunction associated with sepsis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Leukocyte Rolling
  • Liver / blood supply*
  • Liver / pathology
  • Liver / physiopathology
  • Liver Failure / pathology
  • Liver Failure / physiopathology*
  • Male
  • Mice
  • Microcirculation / pathology
  • Microcirculation / physiopathology
  • Multiple Organ Failure / pathology
  • Multiple Organ Failure / physiopathology*
  • Neutrophil Infiltration*
  • Platelet Adhesiveness*
  • Sepsis / pathology
  • Sepsis / physiopathology*