Caspases and nitric oxide broadly regulate dendritic cell maturation and surface expression of class II MHC proteins

Heng Wong Siew, Laura Santambrogio, Jack L. Strominger

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The passage of dendritic cells (DC) from immature to terminally differentiated antigen-presenting cells is accompanied by numerous morphological, phenotypic, and functional changes. These changes include, for example, expression of "empty" class II MHC proteins (MHCII) at the surface in immature DC, whereas a much larger amount of peptide-loaded MHCII is expressed at the surface in mature DC. Here we show that, in cultured immature DC derived from murine bone-marrow precursors, a number of molecules involved in intracellular trafficking were present in a cleaved form, degraded by caspase-like proteases. Cleavage was either inhibited or reduced significantly during maturation of DC induced by either LPS and TNF-α or by peptides that inhibit caspase activities. Inducible nitric oxide (NO) synthetase up-regulated by LPS was essential for inhibiting the caspase-like activity during the maturation of DC. Moreover, treatment with LPS or caspase inhibitor resulted in expression of MHCII/peptide complexes at the cell surface. Thus, the alteration of the endosomal trafficking pathways during the development of DC that parallels the changes in surface expression of MHCII is regulated at least in part by the activities of caspases, inducible NO synthetase, and its product NO.

Original languageEnglish (US)
Pages (from-to)17783-17788
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number51
DOIs
StatePublished - Dec 21 2004

Fingerprint

Caspases
Dendritic Cells
Nitric Oxide
Proteins
Nitric Oxide Synthase
Peptides
Caspase Inhibitors
Antigen-Presenting Cells
Peptide Hydrolases
Bone Marrow

Keywords

  • Antigen presentation
  • Endosomes
  • LPS
  • Nitric oxide synthetase
  • Protease inhibitors

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

@article{63582776ec92428f9082cd6bc98bacf7,
title = "Caspases and nitric oxide broadly regulate dendritic cell maturation and surface expression of class II MHC proteins",
abstract = "The passage of dendritic cells (DC) from immature to terminally differentiated antigen-presenting cells is accompanied by numerous morphological, phenotypic, and functional changes. These changes include, for example, expression of {"}empty{"} class II MHC proteins (MHCII) at the surface in immature DC, whereas a much larger amount of peptide-loaded MHCII is expressed at the surface in mature DC. Here we show that, in cultured immature DC derived from murine bone-marrow precursors, a number of molecules involved in intracellular trafficking were present in a cleaved form, degraded by caspase-like proteases. Cleavage was either inhibited or reduced significantly during maturation of DC induced by either LPS and TNF-α or by peptides that inhibit caspase activities. Inducible nitric oxide (NO) synthetase up-regulated by LPS was essential for inhibiting the caspase-like activity during the maturation of DC. Moreover, treatment with LPS or caspase inhibitor resulted in expression of MHCII/peptide complexes at the cell surface. Thus, the alteration of the endosomal trafficking pathways during the development of DC that parallels the changes in surface expression of MHCII is regulated at least in part by the activities of caspases, inducible NO synthetase, and its product NO.",
keywords = "Antigen presentation, Endosomes, LPS, Nitric oxide synthetase, Protease inhibitors",
author = "Siew, {Heng Wong} and Laura Santambrogio and Strominger, {Jack L.}",
year = "2004",
month = "12",
day = "21",
doi = "10.1073/pnas.0408229102",
language = "English (US)",
volume = "101",
pages = "17783--17788",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "51",

}

TY - JOUR

T1 - Caspases and nitric oxide broadly regulate dendritic cell maturation and surface expression of class II MHC proteins

AU - Siew, Heng Wong

AU - Santambrogio, Laura

AU - Strominger, Jack L.

PY - 2004/12/21

Y1 - 2004/12/21

N2 - The passage of dendritic cells (DC) from immature to terminally differentiated antigen-presenting cells is accompanied by numerous morphological, phenotypic, and functional changes. These changes include, for example, expression of "empty" class II MHC proteins (MHCII) at the surface in immature DC, whereas a much larger amount of peptide-loaded MHCII is expressed at the surface in mature DC. Here we show that, in cultured immature DC derived from murine bone-marrow precursors, a number of molecules involved in intracellular trafficking were present in a cleaved form, degraded by caspase-like proteases. Cleavage was either inhibited or reduced significantly during maturation of DC induced by either LPS and TNF-α or by peptides that inhibit caspase activities. Inducible nitric oxide (NO) synthetase up-regulated by LPS was essential for inhibiting the caspase-like activity during the maturation of DC. Moreover, treatment with LPS or caspase inhibitor resulted in expression of MHCII/peptide complexes at the cell surface. Thus, the alteration of the endosomal trafficking pathways during the development of DC that parallels the changes in surface expression of MHCII is regulated at least in part by the activities of caspases, inducible NO synthetase, and its product NO.

AB - The passage of dendritic cells (DC) from immature to terminally differentiated antigen-presenting cells is accompanied by numerous morphological, phenotypic, and functional changes. These changes include, for example, expression of "empty" class II MHC proteins (MHCII) at the surface in immature DC, whereas a much larger amount of peptide-loaded MHCII is expressed at the surface in mature DC. Here we show that, in cultured immature DC derived from murine bone-marrow precursors, a number of molecules involved in intracellular trafficking were present in a cleaved form, degraded by caspase-like proteases. Cleavage was either inhibited or reduced significantly during maturation of DC induced by either LPS and TNF-α or by peptides that inhibit caspase activities. Inducible nitric oxide (NO) synthetase up-regulated by LPS was essential for inhibiting the caspase-like activity during the maturation of DC. Moreover, treatment with LPS or caspase inhibitor resulted in expression of MHCII/peptide complexes at the cell surface. Thus, the alteration of the endosomal trafficking pathways during the development of DC that parallels the changes in surface expression of MHCII is regulated at least in part by the activities of caspases, inducible NO synthetase, and its product NO.

KW - Antigen presentation

KW - Endosomes

KW - LPS

KW - Nitric oxide synthetase

KW - Protease inhibitors

UR - http://www.scopus.com/inward/record.url?scp=11144230451&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=11144230451&partnerID=8YFLogxK

U2 - 10.1073/pnas.0408229102

DO - 10.1073/pnas.0408229102

M3 - Article

VL - 101

SP - 17783

EP - 17788

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 51

ER -