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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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IL-8 secretion.IL-8 release 24 h after stimulation in response to different stimuli. Cells were cultured in 24 well plates and treated with stimuli in normoxia, hypoxia or after hypoxia for 24 h and then transferred to normoxia and stimulated for 24 h. Supernatants were analysed for the content of IL-8 in three different donors, n = 3, mean ± SEM and * P<0.05, **P<0.01, ***P<0.001.
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pone-0012360-g006: IL-8 secretion.IL-8 release 24 h after stimulation in response to different stimuli. Cells were cultured in 24 well plates and treated with stimuli in normoxia, hypoxia or after hypoxia for 24 h and then transferred to normoxia and stimulated for 24 h. Supernatants were analysed for the content of IL-8 in three different donors, n = 3, mean ± SEM and * P<0.05, **P<0.01, ***P<0.001.

Mentions: Mast cells express CD30 ligand/CD153 and we have previously shown that activation by CD30-Fc fusion protein induces a degranulation-independent release of IL-8 [8]. As a negative control for this experiment we used a CD6-Fc fusion protein. We also measured the release of IL-8 after treatment with LPS and A23197. All three stimuli induced IL-8 secretion both in normoxia, hypoxia and in reoxygenated cultures (Fig. 6). Upon CD30 and LPS treatment the release was significantly attenuated in the hypoxic cultures and the reoxygenated cultures, compared to normoxia (Fig. 6). Thus, although mast cells seem to be less responsive to activating stimuli after hypoxia and even less responsive after reoxygenation, as observed from the IL-8 release data, they are still reactive.


Mast cell survival and mediator secretion in response to hypoxia.

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

IL-8 secretion.IL-8 release 24 h after stimulation in response to different stimuli. Cells were cultured in 24 well plates and treated with stimuli in normoxia, hypoxia or after hypoxia for 24 h and then transferred to normoxia and stimulated for 24 h. Supernatants were analysed for the content of IL-8 in three different donors, n = 3, mean ± SEM and * P<0.05, **P<0.01, ***P<0.001.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0012360-g006: IL-8 secretion.IL-8 release 24 h after stimulation in response to different stimuli. Cells were cultured in 24 well plates and treated with stimuli in normoxia, hypoxia or after hypoxia for 24 h and then transferred to normoxia and stimulated for 24 h. Supernatants were analysed for the content of IL-8 in three different donors, n = 3, mean ± SEM and * P<0.05, **P<0.01, ***P<0.001.
Mentions: Mast cells express CD30 ligand/CD153 and we have previously shown that activation by CD30-Fc fusion protein induces a degranulation-independent release of IL-8 [8]. As a negative control for this experiment we used a CD6-Fc fusion protein. We also measured the release of IL-8 after treatment with LPS and A23197. All three stimuli induced IL-8 secretion both in normoxia, hypoxia and in reoxygenated cultures (Fig. 6). Upon CD30 and LPS treatment the release was significantly attenuated in the hypoxic cultures and the reoxygenated cultures, compared to normoxia (Fig. 6). Thus, although mast cells seem to be less responsive to activating stimuli after hypoxia and even less responsive after reoxygenation, as observed from the IL-8 release data, they are still reactive.

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