Alteraciones en el funcionalismo de los macrófagos del sistema GALT (Gut-Associated Lymphoid Tissue). Relación con la translocación bacteriana y el desarrollo de peritonitis bacteriana espontánea sobre un modelo de cirrosis experimental

Abstract

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a serious complication of decompensated cirrhosis. Bacterial translocation (TB) and immunosuppression associated with cirrhosis play a key role in its development. Immune cells in the gut-associated lymphoid tissue (GALT) play an important role in maintaining intestinal immune response and prevent the entry of pathogens. Antibiotics such as norfloxacin have an immunomodulatory effect that could favour the immune response in patients with decompensated cirrhosis. However, GALT macrophages function in cirrhosis and its involvement in the development of TB and PBE and the effect of norfloxacin on GALT cells is not known. AIMS: To determine in an experimental rat model of cirrhosis and ascites, whether there is a deficiciency and at what level (opsonization, phagocytosis and / or intracellular killing) in the macrophage function of the GALT and ascites. To determine the effect of norfloxacin on these cells. METHODS: A control group (n = 10) and 3 groups of cirrhotic rats with ascites by CCl4 (A: cirrhosis and ascites, n=10; B: cirrhosis and ascites + norfloxacin, n=10; C: cirrhosis+SBP, n=10) were included. Peritoneal lavage / ascites (LA), mesenteric lymph (GM), Peyer's patches (PP) and colonic lamina propria (LP) macrophages were obtained. A cell suspension from every GALT compartment was obtained by mechanical and enzymatic digestion. E.coli phagocytosis of CD11b + macrophages of each compartment, the opsonization effect of a "pool" of cirrhotic rats sera and controls rats sera, and the bactericidal capacity were assessed by flow citometry. TNF-α, IFN-γ, CRP, complement C3, NO and endotoxin plasma levels from each animal were quantified. RESULTS: There were no differences in the phagocytic capacity of macrophages of the different compartments between the 4 groups. Phagocytosis significantly increased when bacteria were opsonized with "pool" of control sera versus "pool" of cirrhotic sera, in all compartments and regardless of the study group. Intracellular Killing was significantly lower in all compartments of the A and C groups compared to control ghroup and was inversely correlated with plasma levels of endotoxin, NO, CRP, TNFα and IFNγ, and directly correlated with levels C3. The administration of norfloxacin significantly improved intracellular killing. CONCLUSIONS: GALT system macrophages functionality is globally impaired in rats with cirrhotic ascites, with a decreased opsonic capacity and intracellular killing. Impaired intracellullar killing correlates with plasma endotoxemia and inflammatory markers. Treatment with norfloxacin partially improves GALT macrophage functionality.

Date of Award	11 Mar 2016
Original language	Undefined/Unknown
Awarding Institution	Germans Trias i Pujol Health Sciences Research Institute (IGTP)
Supervisor	Ramón Planas Vila (Director) & Ramon Bartolí Solé (Director)