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Mast cell survival and mediator secretion in response to hypoxia.

Gulliksson M, Carvalho RF, Ullerås E, Nilsson G - PLoS ONE (2010)

Bottom Line: Hypoxia, per se, did not induce mast cell degranulation, but we observed an increased secretion of IL-6, where autocrine produced IL-6 promoted mast cell survival.Hypoxia did not have any effect on A23187 induced degranulation or secretion of cytokines.This may be of importance for host defence where mast cells in a hypoxic tissue can react to intruders, but also in chronic inflammations where mast cell reactivity is not inhibited by the inflammatory associated hypoxia.

View Article: PubMed Central - PubMed

Affiliation: Clinical Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

ABSTRACT
Tissue hypoxia is a consequence of decreased oxygen levels in different inflammatory conditions, many associated with mast cell activation. However, the effect of hypoxia on mast cell functions is not well established. Here, we have investigated the effect of hypoxia per se on human mast cell survival, mediator secretion, and reactivity. Human cord blood derived mast cells were subjected to three different culturing conditions: culture and stimulation in normoxia (21% O(2)); culture and stimulation in hypoxia (1% O(2)); or 24 hour culture in hypoxia followed by stimulation in normoxia. Hypoxia, per se, did not induce mast cell degranulation, but we observed an increased secretion of IL-6, where autocrine produced IL-6 promoted mast cell survival. Hypoxia did not have any effect on A23187 induced degranulation or secretion of cytokines. In contrast, cytokine secretion after LPS or CD30 treatment was attenuated, but not inhibited, in hypoxia compared to normoxia. Our data suggests that mast cell survival, degranulation and cytokine release are sustained under hypoxia. This may be of importance for host defence where mast cells in a hypoxic tissue can react to intruders, but also in chronic inflammations where mast cell reactivity is not inhibited by the inflammatory associated hypoxia.

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HIF-1α accumulation under hypoxia.HMC-1.2 and CBMC were cultured for 24 h under hypoxia or normoxia. HIF-1α accumulation was determined by western blot. DFX was used as a positive control. The figure is representative of three independent experiments.
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pone-0012360-g003: HIF-1α accumulation under hypoxia.HMC-1.2 and CBMC were cultured for 24 h under hypoxia or normoxia. HIF-1α accumulation was determined by western blot. DFX was used as a positive control. The figure is representative of three independent experiments.

Mentions: Under hypoxic conditions several cellular mechanisms can be activated. The transcription factor HIF-1α is stabilised under low oxygen concentrations and can thus activate a variety of genes involved in the control of cellular metabolism. A mast cell derived cell line, HMC-1.2, and CBMC were cultured for 24h, both under normoxic and hypoxic conditions. As a positive control, we used deferoxamide (DFX), which is a well-described stabiliser of HIF-1α. Both hypoxic conditions and DFX induced an increased accumulation of the HIF-1α protein in both mast cell types tested (Fig. 3).


Mast cell survival and mediator secretion in response to hypoxia.

Gulliksson M, Carvalho RF, Ullerås E, Nilsson G - PLoS ONE (2010)

HIF-1α accumulation under hypoxia.HMC-1.2 and CBMC were cultured for 24 h under hypoxia or normoxia. HIF-1α accumulation was determined by western blot. DFX was used as a positive control. The figure is representative of three independent experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2925952&req=5

pone-0012360-g003: HIF-1α accumulation under hypoxia.HMC-1.2 and CBMC were cultured for 24 h under hypoxia or normoxia. HIF-1α accumulation was determined by western blot. DFX was used as a positive control. The figure is representative of three independent experiments.
Mentions: Under hypoxic conditions several cellular mechanisms can be activated. The transcription factor HIF-1α is stabilised under low oxygen concentrations and can thus activate a variety of genes involved in the control of cellular metabolism. A mast cell derived cell line, HMC-1.2, and CBMC were cultured for 24h, both under normoxic and hypoxic conditions. As a positive control, we used deferoxamide (DFX), which is a well-described stabiliser of HIF-1α. Both hypoxic conditions and DFX induced an increased accumulation of the HIF-1α protein in both mast cell types tested (Fig. 3).

Bottom Line: Hypoxia, per se, did not induce mast cell degranulation, but we observed an increased secretion of IL-6, where autocrine produced IL-6 promoted mast cell survival.Hypoxia did not have any effect on A23187 induced degranulation or secretion of cytokines.This may be of importance for host defence where mast cells in a hypoxic tissue can react to intruders, but also in chronic inflammations where mast cell reactivity is not inhibited by the inflammatory associated hypoxia.

View Article: PubMed Central - PubMed

Affiliation: Clinical Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

ABSTRACT
Tissue hypoxia is a consequence of decreased oxygen levels in different inflammatory conditions, many associated with mast cell activation. However, the effect of hypoxia on mast cell functions is not well established. Here, we have investigated the effect of hypoxia per se on human mast cell survival, mediator secretion, and reactivity. Human cord blood derived mast cells were subjected to three different culturing conditions: culture and stimulation in normoxia (21% O(2)); culture and stimulation in hypoxia (1% O(2)); or 24 hour culture in hypoxia followed by stimulation in normoxia. Hypoxia, per se, did not induce mast cell degranulation, but we observed an increased secretion of IL-6, where autocrine produced IL-6 promoted mast cell survival. Hypoxia did not have any effect on A23187 induced degranulation or secretion of cytokines. In contrast, cytokine secretion after LPS or CD30 treatment was attenuated, but not inhibited, in hypoxia compared to normoxia. Our data suggests that mast cell survival, degranulation and cytokine release are sustained under hypoxia. This may be of importance for host defence where mast cells in a hypoxic tissue can react to intruders, but also in chronic inflammations where mast cell reactivity is not inhibited by the inflammatory associated hypoxia.

Show MeSH
Related in: MedlinePlus