Expression of P-selectin on hepatic endothelia and platelets promoting neutrophil removal by liver macrophages.
The role of P-selectin on polymorphonuclear leukocyte (PMN) adhesion-induced PMN elimination in the liver is unclear. Our objectives were to show the expression and distribution of P-selectin in rat liver, as well as to evaluate the changes in the modulation of the expression of P-selectin and its role in the accumulation and sequestration of PMNs. The intravenous administration of endotoxin markedly increased the expression of P-selectin on the venous and sinusoidal endothelial cells, as well as on the platelets trapped in the liver. Its expression peaked at 6 hours postinjection and was associated with a rapid increase in the aggregation and elimination of PMNs in the hepatic sinusoids. Combined treatment with an antibody to P-selectin or with low molecular weight heparin, a P-selectin antagonist, blocked the P-selectin, significantly reduced the arrest of PMNs, and delayed their removal in the liver. Pretreatment with gadolinium chloride inhibited phagocytosis of PMNs by the Kupffer cells, decreased the expression of P-selectin, and limited the hepatic accumulation of PMNs. Thus, P-selectin played a role in accumulation and elimination of PMNs from the liver. Results also suggest that activated Kupffer cells can modulate the expression of P-selectin in the liver and influence the homeostasis of PMNs in the circulation during acute inflammation.
Shi
J
J
Department of Anatomy, School of Medicine, Tokyo Medical and Dental University, Tokyo 113, Japan.
Kokubo
Y
Y
Wake
K
K
D000818:Animals; D001772:Blood Cell Count; D001792:Blood Platelets / Q000473:pathology* / Q000502:physiology; D004727:Endothelium / Q000473:pathology* / Q000503:physiopathology; D007728:Kupffer Cells / Q000473:pathology*; D008099:Liver / Q000473:pathology* / Q000503:physiopathology*; D008262:Macrophage Activation; D008297:Male; D009504:Neutrophils / Q000473:pathology*; D019007:P-Selectin / Q000502:physiology*; D010587:Phagocytosis; D051381:Rats; D017208:Rats, Wistar
D019007:P-Selectin