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.


CONCLUSIONS
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.
Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
A H
AH
Nissim Ben Efraim
L
L
Karra
M
M
Ben-Zimra
F
F
Levi-Schaffer
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015687:Cell Hypoxia; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
D015703:Antigens, CD; C515070:CD300A protein, human; D011971:Receptors, Immunologic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor