In situ CD14 expression in biliary atresia: Comparison between early and late stages

Ahmed, Abul Faiz Kabir Uddin; Nio, Masaki; Ohtani, Haruo; Nishimura, Hiroshi; Ohi, Ryoji

doi:10.1053/jpsu.2001.20063

Cited by 18 publications

(18 citation statements)

References 12 publications

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“…Expression of major histocompatibility complexes (classes I and II), which is induced by IFN (types I and II, respectively), has also been found to be elevated in BA [23,24]. These and other findings are the basis for the assumption that immune response plays an important role in the etiology of BA [2,25]. In addition, the aspect of an autoimmune reaction, which could be triggered by viral infection or any other causative agent, must also be taken into consideration.…”

Section: Discussionmentioning

confidence: 77%

Expression of the interferon-induced Mx proteins in biliary atresia

Al-Masri

Flemming

Rodeck

et al. 2006

Journal of Pediatric Surgery

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Section: Discussionmentioning

confidence: 77%

Expression of the interferon-induced Mx proteins in biliary atresia

Al-Masri

Flemming

Rodeck

et al. 2006

Journal of Pediatric Surgery

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“…The enriched expression of the lipopolisaccharide receptor CD14 in Kupffer cells and the population of the livers of children with biliary atresia by activated macrophages suggest that these cells contribute to the creation of a pro-inflammatory environment at diagnosis and/or after portoenterostomy (24,25). At least in one report, a greater population of macrophages in the affected liver was associated with poor outcome (25).…”

Section: Discussionmentioning

confidence: 99%

Macrophages Are Targeted by Rotavirus in Experimental Biliary Atresia and Induce Neutrophil Chemotaxis by Mip2/Cxcl2

et al. 2010

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Biliary atresia is an obstructive cholangiopathy of unknown etiology. Although the adaptive immune system has been shown to regulate the obstruction of bile ducts in a rotavirus-induced mouse model, little is known about the virus-induced inflammatory response. Here, we hypothesized that cholangiocytes secrete chemoattractants in response to rotavirus. To test this hypothesis, we infected cholangiocyte and macrophage cell lines with rhesus rotavirus type A (RRV), quantified cytokines and chemokines and measured the migration of splenocytes. We also used PCR and immunostaining to search for new cellular targets of RRV in the liver. We found that RRV-infected cholangiocytes induced the mRNA expression for chemokines, but conditioned media failed to promote chemotaxis of splenocytes. Analyzing livers after viral challenge, we detected RRV in hepatic macrophages and demonstrated that media from RRV-infected macrophages have high concentrations of cytokines and chemokines and induced chemotaxis of neutrophils. Most notably, addition of anti-Mip2/Cxcl2 antibodies depleted this chemokine in the conditioned media and completely prevented neutrophil chemotaxis. In conclusion, infected cholangiocytes did not promote chemotaxis of inflammatory cells. Investigating alternate cellular targets of RRV, we detected the virus in hepatic macrophages and found that infected macrophages promoted neutrophil chemotaxis by release of Mip2/Cxcl2 in response to RRV. (Pediatr Res 67: 345-351, 2010) B iliary atresia, the most common cause of neonatal cholestasis, results from an inflammatory and fibrosing obstruction of extrahepatic bile ducts. The etiology is unknown, but studies in an experimental mouse model of rotavirus-induced biliary atresia indicate that pathogenic mechanisms of disease begin with an injury to the biliary epithelium, followed by a robust inflammatory infiltration of the wall of extrahepatic bile ducts, obstruction of the lumen by inflammatory cells, and final progression to fibrosis (1). These pathologic changes in the liver and extrahepatic bile ducts closely resemble human biliary atresia (2,3). Studies of livers of infants at the time of diagnosis have long recognized an activation of inflammatory cells (4), and a broad analysis of the hepatic gene expression profile identified a prominent proinflammatory signature (5). Disruption of this signature by loss of IFN-␥ or the loss of CD8ϩ lymphocytes in the mouse model largely prevented duct obstruction and the phenotype of experimental biliary atresia (6,7). Interestingly, in vivo depletion of CD4ϩ lymphocytes or the genetic loss of IL-12, or the depletion of TNF-␣ later in the course of biliary injury did not alter the progression to biliary atresia phenotype (7-9), which supported the coexistence of accessory pathways regulating the pathology of extrahepatic bile ducts. Despite the progress in deciphering key elements regulating duct obstruction and atresia, little is known about molecular circuits that are activated in early stages of the disease.Cellu...

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“…Intense staining of CD14 was found on sinusoidal and portal tract macrophages in BA tissue and not found in the portal tracts of control specimens. Furthermore, Ahmed et al (34) compared the in situ expression of CD14 between early and late stages of BA. Almost 70% of BA specimens at time of portoenterostomy had extensive CD14 expression, especially on sinusoidal Kupffer cells.…”

Section: Viral and Other Infectious Agentsmentioning

confidence: 99%