Apoptosis of neutrophils and their elimination by Kupffer cells in rat liver

Abstract

ing of the apoptosis and clearance of neutrophils is limited The fate of neutrophils in the peripheral circulation by difficulties in studying their site-specific accumulation and is poorly understood. In this study, the role of Kupffer in quantifying their physiological cell death in the circulation. cells in eliminating aged and apoptotic neutrophils wasChromatin condensation and DNA fragmentation appear to investigated. Liver, spleen, lung, and blood samples from occur within a few minutes, 14 and the phagocytosis of apoWistar rats were examined by light and electron microsptotic neutrophils leads to their marked degradation, at copy, the terminal deoxynucleotidyl transferase-mediwhich point they are no longer recognizable as neutrophils. ated deoxyuridine triphosphate-biotin nick end labelThis rapidity of apoptosis and subsequent degradation may ing (TUNEL) method, and immunohistochemistry after explain the magnitude of these processes during the resoluthe intravenous injection of OK-432, a streptococcal tion of inflammation 15 and may not be reflected in microscopic preparation. Neutrophils were trapped predominantly observations of static histological sections. Furthermore, in the periportal and midzonal regions of hepatic lobules analysis of DNA fragmentation by gel electrophoresis cannot and were in contact with endothelial cells and Kupffer identify, localize, or quantify apoptosis at the cellular level. cells, or were surrounded by Kupffer cells. The trappingInvestigation of phagocytosis of apoptotic neutrophils in of neutrophils peaked after 6 hours. Apoptotic neutrothe circulation may lead to a greater understanding of the phils, with or without buds, were found in the lumen of physiological and pathological roles of the removal of circulathepatic sinusoids as early as 6 hours, reached maximal ing, senescent neutrophils. The increase in circulating levels after 12 hours, and represented greater than 60% neutrophils is one prerequisite for phagocytosis. The intraof the total number of neutrophils in the liver. The presperitoneal administration of inflammatory mediators, such ence of apoptotic neutrophils was correlated with the as OK-432 or lyophilized streptococcal bacteria, induces the degree of neutrophil phagocytosis. Double-staining accumulation of neutrophils in peritoneal exudates. 16 Intrashowed that TUNEL-positive neutrophils were phagocyvenous administration of these agents causes an inflammatosed or encircled by ED 1 -or ED 2 -positive Kupffer cells.tory reaction in the liver, as judged by the accumulation of In contrast, apoptosis and phagocytosis of neutrophils macrophages and leukocytes. 17,18 Clearly, mononuclear cell were rare in the spleen, lung, and peripheral blood.production must be exactly balanced by their loss to maintain These results suggested that the appearance of apohomeostasis. While a great deal is known about the accumuptotic neutrophils in the hepatic sinusoids and their lation of neutrophils in the liver, much less is understood rapid clearance by Kupffer cells occurs ...

Liver-associated lymphocytes expressing NK1.1 are essential for oral immune tolerance induction in a murine model

“…Antigen-activated Kupffer cells have antigen presentation, phagocytosis, and killing properties via secretion of cytokines, and induce chemotaxis and lymphocyte aggregation. 36,37 In addition, the adult liver contains pluripotent stem cells, giving rise to multiple cell lineages including thymic and extrathymic T cells, granulocytes, and erythroid lineage cells. 4 Indeed, T cells can differentiate extrathymically in an adult liver.…”

Regulation of CD95 (APO-1/Fas) receptor and ligand expression by lipopolysaccharide and dexamethasone in parenchymal and nonparenchymal rat liver cells

“…23,39 Many lymphocytes became apoptotic after treatment with supernatants derived from 24-hour LPS-stimulated KCs or SECs. However, supernatants derived from 48-hour stimulated cells, i.e., for a period that allowed the release not only of CD95L but also of soluble CD95 receptor (Fig.…”

“…21,22 Recent studies have pointed to a role of sinusoidal endothelial and Kupffer cells in the phagocytosis of circulating neutrophils undergoing apoptosis. 23 When Kupffer cells become activated in response to lipopolysaccharide (LPS), they produce a variety of mediators. Among them, TNF-␣ mediates apoptosis in nonparenchymal liver cells, 24 but the role of the CD95/CD95L system is not definitely established.…”

Neutrophils Sequestered in the Liver Suppress the Proinflammatory Response of Kupffer Cells to Systemic Bacterial Infection

“…The number of transfused neutrophils is increased in the peripheral blood and decreased in the livers of animals rendered Kupffer cell deficient before transfusion, supporting the role of Kupffer cells in neutrophil disposal. Shi et al (18,19) found neutrophils inside Kupffer cells in liver sections derived from rats inoculated with bacterial endotoxin or the Streptococcus-derived immunomodulator OK-432. Similarly, macrophages recovered from the livers of mice infected with Listeria monocytogenes contained intracellular neutrophils (4).…”