Effect of lipopolysaccharide (LPS) and peptidoglycan (PGN) on human mast cell numbers, cytokine production, and protease composition

<p>Abstract</p> <p>Background</p> <p>Human mast cell (HuMC) maturation occurs in tissues interfacing with the external environment, exposing both mast cell progenitors and mature mast cells, to bacteria and their products. It is unknown, however, whether long- or short-...

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Main Authors: Wu Yalin, Kulka Marianna, Swindle Emily, Kirshenbaum Arnold S, Metcalfe Dean D
Format: Article
Language:English
Published: BMC 2008-08-01
Series:BMC Immunology
Online Access:http://www.biomedcentral.com/1471-2172/9/45
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author Wu Yalin
Kulka Marianna
Swindle Emily
Kirshenbaum Arnold S
Metcalfe Dean D
author_facet Wu Yalin
Kulka Marianna
Swindle Emily
Kirshenbaum Arnold S
Metcalfe Dean D
author_sort Wu Yalin
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Human mast cell (HuMC) maturation occurs in tissues interfacing with the external environment, exposing both mast cell progenitors and mature mast cells, to bacteria and their products. It is unknown, however, whether long- or short-term exposure to bacteria-derived toll-like receptor (TLR) ligands, such as lipopolysaccharide (LPS) or peptidoglycan (PGN), influences HuMC biology.</p> <p>Results</p> <p>Over 6 wks of culture, LPS had minimal effect on HuMC numbers but increased CD117, tryptase and chymase expression. PGN inhibited HuMC development. For mature mast cells, LPS in the presence of rhSCF (10 ng/ml) increased CD117, tryptase, chymase and carboxypeptidase expression, primarily in CD117<sup>low </sup>HuMC. LPS decreased FcεRI expression and β-hexosaminidase release; but had no effect on LTC<sub>4 </sub>and PGD<sub>2 </sub>production. PGN reduced HuMC numbers; and CD117 and tryptase expression. IL-1β and IL-6 (in addition to IL-8 and IL-12) were detected in short-term culture supernatants of LPS treated cells, and reproduced the increases in CD117, tryptase, chymase, and carboxypeptidase expression observed in the presence of LPS. Comparative studies with mouse bone marrow-derived mast cells from wild type, but not TLR4 knockout mice, showed increases in mRNA of mouse mast cell chymases MMCP-1, MMCP-2 and MMCP-4.</p> <p>Conclusion</p> <p>PGN inhibits HuMC growth, while LPS exerts its primary effects on mature HuMC by altering cytokine production and protease composition, particularly at low concentrations of SCF. These data demonstrate the ability of bacterial products to alter HuMC mediator production, granular content, and number which may be particularly relevant at mucosal sites where HuMC are exposed to these products.</p>
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spelling doaj.art-19e55867d3eb44609b2db711d57a52022022-12-22T03:17:56ZengBMCBMC Immunology1471-21722008-08-01914510.1186/1471-2172-9-45Effect of lipopolysaccharide (LPS) and peptidoglycan (PGN) on human mast cell numbers, cytokine production, and protease compositionWu YalinKulka MariannaSwindle EmilyKirshenbaum Arnold SMetcalfe Dean D<p>Abstract</p> <p>Background</p> <p>Human mast cell (HuMC) maturation occurs in tissues interfacing with the external environment, exposing both mast cell progenitors and mature mast cells, to bacteria and their products. It is unknown, however, whether long- or short-term exposure to bacteria-derived toll-like receptor (TLR) ligands, such as lipopolysaccharide (LPS) or peptidoglycan (PGN), influences HuMC biology.</p> <p>Results</p> <p>Over 6 wks of culture, LPS had minimal effect on HuMC numbers but increased CD117, tryptase and chymase expression. PGN inhibited HuMC development. For mature mast cells, LPS in the presence of rhSCF (10 ng/ml) increased CD117, tryptase, chymase and carboxypeptidase expression, primarily in CD117<sup>low </sup>HuMC. LPS decreased FcεRI expression and β-hexosaminidase release; but had no effect on LTC<sub>4 </sub>and PGD<sub>2 </sub>production. PGN reduced HuMC numbers; and CD117 and tryptase expression. IL-1β and IL-6 (in addition to IL-8 and IL-12) were detected in short-term culture supernatants of LPS treated cells, and reproduced the increases in CD117, tryptase, chymase, and carboxypeptidase expression observed in the presence of LPS. Comparative studies with mouse bone marrow-derived mast cells from wild type, but not TLR4 knockout mice, showed increases in mRNA of mouse mast cell chymases MMCP-1, MMCP-2 and MMCP-4.</p> <p>Conclusion</p> <p>PGN inhibits HuMC growth, while LPS exerts its primary effects on mature HuMC by altering cytokine production and protease composition, particularly at low concentrations of SCF. These data demonstrate the ability of bacterial products to alter HuMC mediator production, granular content, and number which may be particularly relevant at mucosal sites where HuMC are exposed to these products.</p>http://www.biomedcentral.com/1471-2172/9/45
spellingShingle Wu Yalin
Kulka Marianna
Swindle Emily
Kirshenbaum Arnold S
Metcalfe Dean D
Effect of lipopolysaccharide (LPS) and peptidoglycan (PGN) on human mast cell numbers, cytokine production, and protease composition
BMC Immunology
title Effect of lipopolysaccharide (LPS) and peptidoglycan (PGN) on human mast cell numbers, cytokine production, and protease composition
title_full Effect of lipopolysaccharide (LPS) and peptidoglycan (PGN) on human mast cell numbers, cytokine production, and protease composition
title_fullStr Effect of lipopolysaccharide (LPS) and peptidoglycan (PGN) on human mast cell numbers, cytokine production, and protease composition
title_full_unstemmed Effect of lipopolysaccharide (LPS) and peptidoglycan (PGN) on human mast cell numbers, cytokine production, and protease composition
title_short Effect of lipopolysaccharide (LPS) and peptidoglycan (PGN) on human mast cell numbers, cytokine production, and protease composition
title_sort effect of lipopolysaccharide lps and peptidoglycan pgn on human mast cell numbers cytokine production and protease composition
url http://www.biomedcentral.com/1471-2172/9/45
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