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Role of the liver in regulating numbers of circulating neutrophils

J Shi1, G E Gilbert, Y Kokubo

  • 1Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. jialan_shi@hms.harvard.edu

Blood
|August 9, 2001
PubMed

Insights

Neutrophil homeostasis involves P-selectin-mediated liver sequestration by Kupffer cells. This process facilitates the clearance of neutrophils, preventing tissue damage and maintaining immune balance.

Area of Science:

  • Immunology
  • Hematology
  • Cell Biology

Background:

  • Neutrophils (polymorphonuclear leukocytes [PMNs]) possess destructive enzymes, crucial for fighting infection but capable of damaging host tissues.
  • The short half-life of PMNs (6 hours) necessitates efficient clearance mechanisms, the details of which remain largely unknown.

Purpose of the Study:

  • To elucidate the mechanisms governing neutrophil homeostasis and clearance in a rat model of endotoxemia.
  • To investigate the role of P-selectin, Kupffer cells, and apoptotic pathways in PMN clearance.

Main Methods:

  • Utilized a rat model of endotoxemia.
  • Investigated P-selectin expression in hepatic sinusoids and veins.
  • Administered gadolinium chloride (GdCl(3)) to inactivate Kupffer cells.
  • Blocked Fas protein and used annexin V to bind phosphatidylserine (PS).

Main Results:

  • P-selectin was upregulated in liver vasculature, mediating Kupffer cell phagocytosis of PMNs.
  • Apoptotic PMNs accumulated in lungs and spleen only after Kupffer cell inactivation.
  • Fas blocking reduced hepatic apoptotic cells; annexin V binding reduced Kupffer cell phagocytosis.

Conclusions:

  • A novel clearance pathway for neutrophils involves P-selectin-mediated sequestration in the liver by Kupffer cells.
  • Kupffer cell phagocytosis, apoptosis, and P-selectin are critical components of neutrophil homeostasis.
  • This mechanism prevents uncontrolled PMN activity and potential tissue damage.

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