The inflammatory response in pediatric biliary disease: Macrophage phenotype and distribution

Tracy, Thomas F.; Dillon, Peter W.; Fox, Eben S.; Minnick, Kathleen; Vogler, Carole

doi:10.1016/s0022-3468(96)90333-4

Cited by 71 publications

(41 citation statements)

References 19 publications

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“…Several human BA studies have documented the influx of macrophages [11,[24][25][26] into portal tracts and we have recently reported up-regulation of TNF-α mRNA expression in livers of BA infants [11]. The relationship of macrophages with bile duct injury has also been shown in other human biliary diseases.…”

Section: Discussionmentioning

confidence: 59%

Armed CD4+ Th1 effector cells and activated macrophages participate in bile duct injury in murine biliary atresia

Mack

Tucker

Sokol

et al. 2005

Clinical Immunology

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Biliary atresia (BA) is an inflammatory cholangiopathy of infancy. A proposed mechanism regarding the pathogenesis of BA is that of a virus-induced, immune-mediated injury to bile ducts. The rotavirus (RRV)-induced murine model of BA was utilized to determine the hepatic inflammatory response related to ductal obstruction and if the immune response recapitulated human BA. One week after infection, there was a significant increase in liver CD4 + T cells producing IFN-γ and in macrophages producing TNF-α. The intrahepatic pattern of inflammation evolved rapidly from an initial predominant CD4 + Th1 cellular response to a subsequent influx of activated macrophages producing TNF-α and iNOS. This immune response persisted despite viral clearance and was representative of the hepatic immune profile present in human BA. Utilization of the murine model of BA yielded mechanistic data that can provide much needed insight into the role played by different arms of the immune system related to the pathogenesis of human BA.

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Section: Discussionmentioning

confidence: 59%

Armed CD4+ Th1 effector cells and activated macrophages participate in bile duct injury in murine biliary atresia

Mack

Tucker

Sokol

et al. 2005

Clinical Immunology

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“…One step removed from this initial phase is activation, infiltration and proliferation of macrophage/monocytes (producing IL-18 and TNF␣), which are able to initiate fibrosis, and produce or control changes in the extracellular matrix. 10 We postulated that established immune / inflammatory activity within the liver involves the release of various soluble mediators and is therefore likely to be paralleled by a circulating component. There have been few reports where soluble cytokines have been measured in BA.…”

Section: Discussionmentioning

confidence: 99%

“…The inflammatory process within the liver is characterized by an initial small cell infiltrate of predominantly CD4ϩ T and natural killer (NK) CD56ϩ lymphocytes 1,2 with a later appearance of cells of the CD68ϩ monocyte/macrophage lineage. 1,3,4 There is also abnormally increased expression of cellular adhesion molecules (CAMs) such as intercellular adhesion molecule (ICAM, CD54), vascular cell adhesion molecule (VCAM, CD106) and E-Selectin (CD62E) on both biliary and vascular endothelium. [1][2][3][4][5] We have also shown abnormally high levels of circulating soluble adhesion molecules (sICAM-1 and sVCAM-1) at the time of Kasai portoenterostomy (KP), with the former having a significant positive correlation with post-natal age and the latter prognostic significance when elevated (Ͼ1380 ng/ml).…”

mentioning

confidence: 99%

“…1,3,4 There is also abnormally increased expression of cellular adhesion molecules (CAMs) such as intercellular adhesion molecule (ICAM, CD54), vascular cell adhesion molecule (VCAM, CD106) and E-Selectin (CD62E) on both biliary and vascular endothelium. [1][2][3][4][5] We have also shown abnormally high levels of circulating soluble adhesion molecules (sICAM-1 and sVCAM-1) at the time of Kasai portoenterostomy (KP), with the former having a significant positive correlation with post-natal age and the latter prognostic significance when elevated (Ͼ1380 ng/ml). 2 The aim of this study was to follow the course of the inflammatory process as expressed by levels of soluble cellular adhesion molecules (CAMs) and cytokines into the early post-operative phase of this disease.…”

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confidence: 99%

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Serial circulating markers of inflammation in biliary atresia—Evolution of the post-operative inflammatory process

et al. 2007

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Biliary atresia (BA) may be characterized as an occlusive cholangiopathy affecting both intraand extra-hepatic parts of the biliary tree, together with a pronounced inflammatory response consisting of hepatic infiltration of (predominantly) CD4؉ lymphocytes and macrophages. Soluble cellular adhesion molecules are also known to be raised at the time of portoenterostomy, presumably reflecting intrahepatic disease. We investigated this measur-

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“…[1][2][3][4] Because of the progressive nature of this disease, up to 80% of BA patients will eventually require liver transplantation for survival, and therefore it is the most common indication for liver transplantation in children. 5 A recent study has shown that of the 20% or so who are alive with their native liver for at least 20 years after the portoenterostomy, progressive bile duct injury and subsequent biliary cirrhosis is present in more than 95% of these patients.…”

mentioning

confidence: 99%

Cellular and humoral autoimmunity directed at bile duct epithelia in murine biliary atresia

et al. 2006

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Biliary atresia is an inflammatory fibrosclerosing lesion of the bile ducts that leads to biliary cirrhosis and is the most frequent indication for liver transplantation in children. The pathogenesis of biliary atresia is not known; one theory is that of a virus-induced, subsequent autoimmune-mediated injury of bile ducts. The aim of this study was to determine whether autoreactive T cells and autoantibodies specific to bile duct epithelia are present in the rotavirus (RRV)-induced murine model of biliary atresia and whether the T cells are sufficient to result in bile duct inflammation. In vitro analyses showed significant increases in IFN-␥-producing T cells from RRV-diseased mice in response to bile duct epithelial autoantigen. Adoptive transfer of the T cells from RRV-diseased mice into naïve syngeneic SCID recipients resulted in bile duct-specific inflammation. This induction of bile duct pathology occurred in the absence of detectable virus, indicating a definite response to bile duct autoantigens. Furthermore, periductal immunoglobulin deposits and serum antibodies reactive to bile duct epithelial protein were detected in RRV-diseased mice. In conclusion, both cellular and humoral components of autoimmunity exist in murine biliary atresia, and the progressive bile duct injury is due in part to a bile duct epithelia-specific T cell-mediated immune response. The role of cellular and humoral autoimmunity in human biliary atresia and possible interventional strategies therefore should be the focus of future research.

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The inflammatory response in pediatric biliary disease: Macrophage phenotype and distribution

Cited by 71 publications

References 19 publications

Armed CD4+ Th1 effector cells and activated macrophages participate in bile duct injury in murine biliary atresia

Armed CD4+ Th1 effector cells and activated macrophages participate in bile duct injury in murine biliary atresia

Serial circulating markers of inflammation in biliary atresia—Evolution of the post-operative inflammatory process

Cellular and humoral autoimmunity directed at bile duct epithelia in murine biliary atresia

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