Role of galectin-3 in classical and alternative macrophage activation in the liver following acetaminophen intoxication.
نویسندگان
چکیده
Inflammatory macrophages have been implicated in hepatotoxicity induced by the analgesic acetaminophen (APAP). In these studies, we characterized the phenotype of macrophages accumulating in the liver following APAP intoxication and evaluated the role of galectin-3 (Gal-3) in macrophage activation. Administration of APAP (300 mg/kg, i.p.) to wild-type mice resulted in the appearance of two distinct subpopulations of CD11b(+) cells in the liver, which expressed high or low levels of the monocyte/macrophage activation marker Ly6C. Whereas CD11b(+)/Ly6C(hi) macrophages exhibited a classically activated proinflammatory phenotype characterized by increased expression of TNF-α, inducible NO synthase, and CCR2, CD11b(+)/Ly6C(lo) macrophages were alternatively activated, expressing high levels of the anti-inflammatory cytokine IL-10. APAP intoxication was also associated with an accumulation of Gal-3(+) macrophages in the liver; the majority of these cells were Ly6C(hi). APAP-induced increases in CD11b(+)/Ly6C(hi) macrophages were significantly reduced in Gal-3(-/-) mice. This reduction was evident 72 h post APAP and was correlated with decreased expression of the classical macrophage activation markers, inducible NO synthase, IL-12, and TNF-α, as well as the proinflammatory chemokines CCL2 and CCL3, and chemokine receptors CCR1 and CCR2. Conversely, numbers of CD11b(+)/Ly6C(lo) macrophages increased in livers of APAP-treated Gal-3(-/-) mice; this was associated with increased expression of the alternative macrophage activation markers Ym1 and Fizz1, increased liver repair, and reduced hepatotoxicity. These data demonstrate that both classically and alternatively activated macrophages accumulate in the liver following APAP intoxication; moreover, Gal-3 plays a role in promoting a persistent proinflammatory macrophage phenotype.
منابع مشابه
Liver following Acetaminophen Intoxication Alternative Macrophage Activation in the Role of Galectin-3 in Classical and
متن کامل
Regulation of alternative macrophage activation by galectin-3.
Alternative macrophage activation is implicated in diverse disease pathologies such as asthma, organ fibrosis, and granulomatous diseases, but the mechanisms underlying macrophage programming are not fully understood. Galectin-3 is a carbohydrate-binding lectin present on macrophages. We show that disruption of the galectin-3 gene in 129sv mice specifically restrains IL-4/IL-13-induced alternat...
متن کاملTemporal Characterization of Microglia/Macrophage Phenotypes in a Mouse Model of Neonatal Hypoxic-Ischemic Brain Injury
Immune cells display a high degree of phenotypic plasticity, which may facilitate their participation in both the progression and resolution of injury-induced inflammation. The purpose of this study was to investigate the temporal expression of genes associated with classical and alternative polarization phenotypes described for macrophages and to identify related cell populations in the brain ...
متن کاملModulating Role of Panax Ginseng in Phase - II Reaction of Hepato - Biotransformation in Albino Rats Following Mercuric Chloride Intoxication
Introduction: The fate of xenobiotics that is present, increasing day by day. The increasing fates altered or inhibit the metabolic activities like detoxification and biotransformation. Methods: The present study highlights this slow biotransformation and detoxification on the basis of specific enzymes which have a say in assessment of mercuric chloride toxicity and modulation by Panax ginse...
متن کاملSingle administrations of high and low doses of acetaminophen causes different effects on COX-2 gene expression and on tissue damage in liver and kidneys
Introduction: High dose of acetaminophen (APAP) is known to have hepatotoxic and nephrotoxic effects and studies show that this toxicities are dependent on the function of phase I bioactivation enzymes- Cyp450- and phase II biotransformation enzymes especially glucuronosylation and sulfonation pathways. However, the role of cyclooxygenase (COX) as an inflammatory mediator in toxic effects of AP...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Journal of immunology
دوره 189 12 شماره
صفحات -
تاریخ انتشار 2012