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% O2); culture and stimulation in hypoxia (1% O2); 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.
Highlights
Mast cells have an important role in many inflammatory diseases, such as asthma, and they are involved in response to infections, tumor progression and in conditions related to ischemia [1,2]
In this study we have investigated the effect of hypoxia (1% O2) per se on human mast cell survival, degranulation and cytokine secretion
Mast cell survival is sustained under hypoxia First we investigated the effect of hypoxia (1% O2) on mast cell viability
Summary
Mast cells have an important role in many inflammatory diseases, such as asthma, and they are involved in response to infections, tumor progression and in conditions related to ischemia [1,2]. Mast cells are distributed in all vascularised tissues throughout the body and more abundantly in tissues exposed to the environment, i.e., lung, gut and skin. This makes them one of the first cells exposed to allergens, pollutants and pathogens [3]. Hypoxia is a prominent feature of inflamed tissues; including tumors, myocardial infarcts, atherosclerotic plaques, lung of asthmatics, healing wounds and sites of bacterial infections. Several of these conditions are associated with increased number of mast cells [6]. In contrast to the effect of hypoxia on macrophage functions that is well documented [7], the effect of hypoxia on mast cell functions is poorly investigated
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