Abstract
BackgroundHuman 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.ResultsOver 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 CD117low HuMC. LPS decreased FcεRI expression and β-hexosaminidase release; but had no effect on LTC4 and PGD2 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.ConclusionPGN 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.
Highlights
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
Mast cell growth and development may occur in a tissue that interfaces with the external environment, potentially exposing HuMC during their development to bacterial products which could have an impact on their subsequent behavior
Effect of LPS and PGN on progenitor HuMC in 6 wk cultures To determine the effect of LPS or PGN over 6 wks on HuMC growth and development, 10–1000 ng/ml LPS or 10–1000 μg/ml PGN was added to CD34+ cultures containing 100 ng/ml recombinant human stem cell factor (rhSCF)
Summary
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, whether long- or short-term exposure to bacteria-derived tolllike receptor (TLR) ligands, such as lipopolysaccharide (LPS) or peptidoglycan (PGN), influences HuMC biology. Mast cell growth and development may occur in a tissue that interfaces with the external environment, potentially exposing HuMC during their development to bacterial products which could have an impact on their subsequent behavior Consistent with this idea is the observation that HuMC have been shown to express Toll-like receptors (TLR) 1–7, and 9 both in vitro and in vivo (lung) [3]; and exposure to such bacterial products as endotoxin (lipopolysaccharide; LPS) or peptidoglycan (PGN) leads to expression and release of TNF-α, GM-CSF, IL-1, IL-5, IL10, IL-13 and IL-15 [4,5,6].
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