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

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

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Purpose: Extrahepatic biliary obstruction in infants and children leads to ductal hyperplasia and portal fibrosis. Inflammatory mediators responsible for increased cellular proliferation and matrix deposition are hypothesized to result from the intrahepatic recruitment and activation of lymphocytes and macrophages (M∅). The authors previously showed components of this mechanism in studies that demonstrated increased adhesion molecule expression in biliary atresia, as well as evidence of altered hepatic M∅ function during the course of experimental cholestatic liver injury. Therefore they sought to determine the expression of macrophage receptor markers CD68 and CD14 in pediatric biliary disease. Methods: Sixteen liver specimens were snap-frozen and cryosectioned onto polylysine-coated slides. Sections were stained with murine monoclonal antibodies to CD68 (resident M∅) and CD14 (monocyte-M∅ lipopolysaccharide [LPS] receptor) glycoproteins. The sections were analyzed using a semiquantitative scale of proliferation and were position-graded from 0 to 3 (maximal). Results: Blinded analysis showed that marked proliferation of CD68-positive cells occurred in five of the six patients with biliary atresia (BA) and in one patient who had severe cholestasis. Normal perisinusoidal liver M∅ were found in specimens from patients with hepatitis (2), choledochal cyst (1), and congenital hepatic fibrosis (1). Similarly, expression of CD14 periportal M∅ was found only in patients with BA or cholestasis (1.9 ± 0.3 [mean ± SEM]) and was absent in other diseases. Strong sinusoidal expression of CD14 was evident in all patients who had extrahepatic biliary obstruction. An early biopsy specimen from a premature infant with BA did not show cholestasis, fibrosis, CD68 M∅ proliferation, or CD14 expression; however, another biopsy specimen, obtained further in the course of jaundice, showed the progressive development of all features. Conclusion: These findings suggest proliferation of resident M∅ in association with cholestasis. The presence of the LPS receptor on periportal cells during cholestatic liver injury points to a potential source of cytokines responsible for the inflammatory reaction of biliary atresia.

Original languageEnglish (US)
Pages (from-to)121-126
Number of pages6
JournalJournal of pediatric surgery
Volume31
Issue number1
DOIs
StatePublished - Jan 1 1996

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Biliary Atresia
Cholestasis
Macrophages
Pediatrics
Phenotype
CD14 Antigens
Liver
Fibrosis
Choledochal Cyst
Biopsy
Polylysine
Macrophage Activation
Wounds and Injuries
Lymphocyte Activation
Jaundice
Premature Infants
Hepatitis
Hyperplasia
Monocytes
Glycoproteins

All Science Journal Classification (ASJC) codes

  • Surgery
  • Pediatrics, Perinatology, and Child Health

Cite this

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title = "The inflammatory response in pediatric biliary disease: Macrophage phenotype and distribution",
abstract = "Purpose: Extrahepatic biliary obstruction in infants and children leads to ductal hyperplasia and portal fibrosis. Inflammatory mediators responsible for increased cellular proliferation and matrix deposition are hypothesized to result from the intrahepatic recruitment and activation of lymphocytes and macrophages (M∅). The authors previously showed components of this mechanism in studies that demonstrated increased adhesion molecule expression in biliary atresia, as well as evidence of altered hepatic M∅ function during the course of experimental cholestatic liver injury. Therefore they sought to determine the expression of macrophage receptor markers CD68 and CD14 in pediatric biliary disease. Methods: Sixteen liver specimens were snap-frozen and cryosectioned onto polylysine-coated slides. Sections were stained with murine monoclonal antibodies to CD68 (resident M∅) and CD14 (monocyte-M∅ lipopolysaccharide [LPS] receptor) glycoproteins. The sections were analyzed using a semiquantitative scale of proliferation and were position-graded from 0 to 3 (maximal). Results: Blinded analysis showed that marked proliferation of CD68-positive cells occurred in five of the six patients with biliary atresia (BA) and in one patient who had severe cholestasis. Normal perisinusoidal liver M∅ were found in specimens from patients with hepatitis (2), choledochal cyst (1), and congenital hepatic fibrosis (1). Similarly, expression of CD14 periportal M∅ was found only in patients with BA or cholestasis (1.9 ± 0.3 [mean ± SEM]) and was absent in other diseases. Strong sinusoidal expression of CD14 was evident in all patients who had extrahepatic biliary obstruction. An early biopsy specimen from a premature infant with BA did not show cholestasis, fibrosis, CD68 M∅ proliferation, or CD14 expression; however, another biopsy specimen, obtained further in the course of jaundice, showed the progressive development of all features. Conclusion: These findings suggest proliferation of resident M∅ in association with cholestasis. The presence of the LPS receptor on periportal cells during cholestatic liver injury points to a potential source of cytokines responsible for the inflammatory reaction of biliary atresia.",
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The inflammatory response in pediatric biliary disease : Macrophage phenotype and distribution. / Tracy, Thomas F.; Dillon, Peter; Fox, Eben S.; Minnick, Kathleen; Vogler, Carole.

In: Journal of pediatric surgery, Vol. 31, No. 1, 01.01.1996, p. 121-126.

Research output: Contribution to journalArticle

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T1 - The inflammatory response in pediatric biliary disease

T2 - Macrophage phenotype and distribution

AU - Tracy, Thomas F.

AU - Dillon, Peter

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AU - Minnick, Kathleen

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N2 - Purpose: Extrahepatic biliary obstruction in infants and children leads to ductal hyperplasia and portal fibrosis. Inflammatory mediators responsible for increased cellular proliferation and matrix deposition are hypothesized to result from the intrahepatic recruitment and activation of lymphocytes and macrophages (M∅). The authors previously showed components of this mechanism in studies that demonstrated increased adhesion molecule expression in biliary atresia, as well as evidence of altered hepatic M∅ function during the course of experimental cholestatic liver injury. Therefore they sought to determine the expression of macrophage receptor markers CD68 and CD14 in pediatric biliary disease. Methods: Sixteen liver specimens were snap-frozen and cryosectioned onto polylysine-coated slides. Sections were stained with murine monoclonal antibodies to CD68 (resident M∅) and CD14 (monocyte-M∅ lipopolysaccharide [LPS] receptor) glycoproteins. The sections were analyzed using a semiquantitative scale of proliferation and were position-graded from 0 to 3 (maximal). Results: Blinded analysis showed that marked proliferation of CD68-positive cells occurred in five of the six patients with biliary atresia (BA) and in one patient who had severe cholestasis. Normal perisinusoidal liver M∅ were found in specimens from patients with hepatitis (2), choledochal cyst (1), and congenital hepatic fibrosis (1). Similarly, expression of CD14 periportal M∅ was found only in patients with BA or cholestasis (1.9 ± 0.3 [mean ± SEM]) and was absent in other diseases. Strong sinusoidal expression of CD14 was evident in all patients who had extrahepatic biliary obstruction. An early biopsy specimen from a premature infant with BA did not show cholestasis, fibrosis, CD68 M∅ proliferation, or CD14 expression; however, another biopsy specimen, obtained further in the course of jaundice, showed the progressive development of all features. Conclusion: These findings suggest proliferation of resident M∅ in association with cholestasis. The presence of the LPS receptor on periportal cells during cholestatic liver injury points to a potential source of cytokines responsible for the inflammatory reaction of biliary atresia.

AB - Purpose: Extrahepatic biliary obstruction in infants and children leads to ductal hyperplasia and portal fibrosis. Inflammatory mediators responsible for increased cellular proliferation and matrix deposition are hypothesized to result from the intrahepatic recruitment and activation of lymphocytes and macrophages (M∅). The authors previously showed components of this mechanism in studies that demonstrated increased adhesion molecule expression in biliary atresia, as well as evidence of altered hepatic M∅ function during the course of experimental cholestatic liver injury. Therefore they sought to determine the expression of macrophage receptor markers CD68 and CD14 in pediatric biliary disease. Methods: Sixteen liver specimens were snap-frozen and cryosectioned onto polylysine-coated slides. Sections were stained with murine monoclonal antibodies to CD68 (resident M∅) and CD14 (monocyte-M∅ lipopolysaccharide [LPS] receptor) glycoproteins. The sections were analyzed using a semiquantitative scale of proliferation and were position-graded from 0 to 3 (maximal). Results: Blinded analysis showed that marked proliferation of CD68-positive cells occurred in five of the six patients with biliary atresia (BA) and in one patient who had severe cholestasis. Normal perisinusoidal liver M∅ were found in specimens from patients with hepatitis (2), choledochal cyst (1), and congenital hepatic fibrosis (1). Similarly, expression of CD14 periportal M∅ was found only in patients with BA or cholestasis (1.9 ± 0.3 [mean ± SEM]) and was absent in other diseases. Strong sinusoidal expression of CD14 was evident in all patients who had extrahepatic biliary obstruction. An early biopsy specimen from a premature infant with BA did not show cholestasis, fibrosis, CD68 M∅ proliferation, or CD14 expression; however, another biopsy specimen, obtained further in the course of jaundice, showed the progressive development of all features. Conclusion: These findings suggest proliferation of resident M∅ in association with cholestasis. The presence of the LPS receptor on periportal cells during cholestatic liver injury points to a potential source of cytokines responsible for the inflammatory reaction of biliary atresia.

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