Role of the liver in regulating numbers of circulating neutrophils

Neutrophils (polymorphonuclear leukocytes [PMNs]) carry potent destructive enzymes that can destroy invasive bacteria or damage normal tissue. PMNs ha ve a half-life of only 6 hours in the blood, but the details of this homeos tasis are unknown. In a rat model of endotoxemia, P-selectin was selectivel y up-regulated in hepatic sinusolds and veins where it was necessary for ph agocytosis of PMNs by Kupffer cells in the liver, as opposed to the spleen or the lungs. Apoptotic PMNs appeared in the lungs and spleen only after in activation of Kupffer cells by gadolinium chloride (GdCl3). Blocking of Fas protein reduced the number of apoptotic cells in the liver; binding of ann exin V to phosphatidylserine (PS) reduced the number of PMNs phagocytosed b y Kupffer cells. The results support a clearance pathway in which apoptosis and phagocytosis are effected by Kupffer cells after P-selectin-mediated s equestration.