Kupffer Cell Production of Cytokine–Induced Neutrophil Chemoattractant Following Ischemia/Reperfusion Injury in Rats

Abstract

We investigated the role of hepatic macrophages in the inflammatory response following reperfusion injury by blocking Kupffer cell phagocytosis with gadolinium chloride (GdCl3). Liver ischemia was induced in rats by occluding the portal vein for 30 minutes. A bolus of GdCl3 (7 mg/kg) was injected intravenously 1 and 2 days before surgery. The serum levels of cytokine-induced neutrophil chemoattractant (CINC) in untreated rats increased following reperfusion, peaked after 6 hours, and then gradually decreased. GdCl3 or heparin alone significantly decreased the serum levels of CINC (P < .05). In addition, pretreatment with GdCl3/heparin further inhibited the rise in the serum levels of CINC following reperfusion compared with those in untreated animals (P < .01). The in vitro production of CINC by Kupffer cells, obtained from animals pretreated with heparin or GdCl3, was significantly lower than that of cells isolated from untreated animals. Pretreatment with GdCl3/heparin further decreased CINC production by Kupffer cells compared with that of cells from animals that were pretreated with heparin or GdCl3 alone. The expression of CINC transcripts in Kupffer cells or in liver tissue peaked 3 hours after reperfusion in untreated animals. Pretreatment with heparin, GdCl3, or both significantly decreased the levels of CINC messenger RNA (mRNA) transcripts. Pretreatment with heparin, GdCl3, or GdCl3/heparin significantly decreased the number of neutrophils that accumulated in the liver 24 hours following reperfusion, compared with those in untreated animals. These results suggest that Kupffer cells release CINC and may play an important role in early neutrophil infiltration into the liver following ischemia/reperfusion.

Cold liver ischemia-reperfusion injury critically depends on liver T cells and is improved by donor pretreatment with interleukin 10 in mice

“…These cells are a major source of ROIs, proinflammatory cytokines or chemokines that promote neutrophils recruitment, adhe- sion, and activation eventually leading to organ injury. 7,8,[47][48][49][50][51][52] Evidence for this role of Kupffer cells includes the protective effect of their deactivation in liver warm ischemia or liver transplantation models. However, the primary events involved in Kupffer-cell activation are currently poorly defined.…”

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.…”

Increased expression of midkine in the rat colon during healing of experimental colitis

“…After changing the DMEM with 2% FBS, the first group was left alone to serve as a control, whereas the other three were incubated with 10 ng/ml of rat recombinant IL-1␤ (Genzyme-Techne, Minneapolis, MN), 50 ng/ml of rat recombinant tumor necrosis factor (TNF)-␣ (Peprotech EC, London, UK), or 40 ng/ml of rat recombinant CINC2-␤ (Peprotech EC). In rats, CINC2-␤ is the human IL-8 homolog, which is produced by the cells in inflamed sites in various tissues and acts as a potent chemotactic agent and mediator of inflammation (9,48). Each group of cells was incubated for 3, 6, 12, 24, or 48 h before total RNA was extracted.…”