The inhibitory receptor CD300a is up-regulated by hypoxia and GM-CSF in human peripheral blood eosinophils.

BACKGROUND: Eosinophils are involved in several inflammatory processes including allergic inflammation. It has been shown that eosinophil functions may be regulated by activating or inhibitory receptors. Hypoxia is a feature of inflamed tissues and has recently been shown to regulate eosinophil viability and pro-angiogenic potential. In this study, the effect of hypoxia and GM-CSF on the inhibitory receptor CD300a in human peripheral blood eosinophils was investigated. METHODS: CD300a expression on eosinophils was analyzed by flow cytometry and evaluated by immuno-fluorescence; mRNA levels were evaluated by RT-PCR. RESULTS: An increase in the expression of CD300a was observed in hypoxic eosinophils compared to the normoxic ones. GM-CSF strongly induced CD300a increase also after 3 h in culture. In addition, hypoxia augmented mRNA levels of CD300a. Inhibition of hypoxia-inducible factor (HIF)-1 abolished the hypoxia-/GM-CSF-induced CD300a increase. CONCLUSION: CD300a expression is up-regulated by hypoxia, and GM-CSF where HIF-1 might play an important role. These results are important for the understanding of eosinophils behavior in inflamed tissue and suggest a new effect on their function in allergic inflammation. Taken together our data point out CD300a as a novel target for the treatment of allergy.

Lipoxin B4 promotes the resolution of allergic inflammation in the upper and lower airways of mice.

Chronic mucosal inflammation is the hallmark of important and common airway diseases, such as allergic rhinitis (AR) and asthma. Lipoxin A4 (LXA4) is an endogenous pro-resolving mediator for mucosal inflammation that decreases allergic and asthmatic responses. Lipoxin B4 (LXB4) is a structurally distinct member of the lipoxin family that signals in a manner distinct from LXA4. LXB4 is generated by mucosal tissues, but its actions in allergic inflammation are unknown. Here, we used murine models of AR and asthma to investigate LXB4's activity in mucosal inflammation. In the upper airway, LXB4 significantly decreased nasal mucosal leukocytes and degranulation of mast cells (MCs) and eosinophils. In the lower airway, LXB4 significantly decreased airway inflammation, mucus metaplasia, and hyper-responsiveness. Inhibition of MC degranulation in vivo by LXB4 was more potent than dexamethasone, and these agents displayed unique profiles for cytokine regulation; however, their overall anti-inflammatory actions were comparable. LXB4 decreased eotaxin-dependent eosinophil chemotaxis, IgE-mediated MC degranulation, and expression of type 2 cytokine receptors. Together, these findings indicate that LXB4 carries cell type selective and mucosal protective actions that broaden the lipoxin family's therapeutic potential for upper and lower airway catabasis.