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Mast cell-derived t...
Mast cell-derived tumour necrosis factor-alpha mediates macrophage inflammatory protein-2-induced recruitment of neutrophils in mice.
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- Wang, Yusheng (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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- Thorlacius, Henrik (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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(creator_code:org_t)
- 2009-01-29
- 2005
- Engelska.
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Ingår i: British Journal of Pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 145:8, s. 1062-1068
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Abstract
Ämnesord
Stäng
- 1 Recent studies have indicated that mast cells play an intermediate role in chemokine-induced neutrophil recruitment in vivo. 2 The aim of the present investigation was to determine the role of tumour necrosis factor-alpha (TNF-alpha) in neutrophil recruitment provoked by the CXC chemokine macrophage inflammatory protein-2 (MIP-2). For this purpose, we used mast cell- and TNF-alpha-deficient mice and studied neutrophil adhesion to endothelial cells in vitro and neutrophil recruitment in the mouse cremaster muscle in vivo. 3 In contrast to the classical chemoattractant formyl-methionine-leucine-phenylalanin ( fMLP), MIP-2 dose dependently increased neutrophil accumulation in vivo. This MIP-2-regulated neutrophil recruitment was abolished in mast cell- deficient mice. 4 TNF-alpha increased E-selectin mRNA expression in both wild-type (WT) and mast cell-deficient mice. In contrast, MIP-2 challenge increased gene expression of E-selectin in WT but not in mast cell-deficient animals. Moreover, MIP-2-provoked extravascular accumulation of neutrophils was reduced by 78% in mice lacking TNF-alpha. 5 In order to better define the role of mast cell-derived TNF-alpha in neutrophil responses to MIP-2, we used an in vitro endothelial cell adhesion assay with and without mast cells. Interestingly, MIP-2-induced neutrophil adhesion to endothelial cells was decreased by 58% using TNF-alpha-deficient compared to WT mast cells. Moreover, mast cell secretion of TNF-alpha increased by more than 71% in response to challenge with MIP-2. 6 Taken together, our results suggest that MIP-2-induced neutrophil recruitment is mediated by TNF-alpha released from local mast cells. These findings help to explain the complex molecular interactions between chemokines, mast cell activation and neutrophil infiltration in vivo.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- mast cells
- adhesion
- chemokines
- migration
- leukocytes
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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