Abstract
Human basophils are an accessible participant of the human allergic reaction. There is natural variation in various functional endpoints and in signaling molecule expression but there has been only a limited effort to place this information in the context of mRNA expression profiles. This study examined the hypothesis that unique mRNA signatures could be identified during the response of human basophils to several known forms of stimulation. Highly purified human basophils were cultured in vitro and exposed to IL-3, IL-5, NGF, IL-33, IL-2, anti-IgE Ab, or FMLP and the mRNA profiles examined by microarrays. The response to IL-3 and anti-IgE Ab were examined on 2–3 time frames and the response to IL-3 examined at several concentrations. In addition, the mRNA signatures of 3 different potential phenotypes were examined. These included basophils with the so-called non-releaser phenotype, and basophils from atopic and non-atopic subjects. Given the role of IL-3 in basophil maturation and the known profound effects on mature basophil function, it was not surprising that IL-3 showed the greatest influence on the basophil transcriptome. However, it also became apparent that the act of isolating and culturing basophils was sufficient to induce a large number of changes in the transcriptome, despite high viability and recovery. These “culture-effect” changes dominated the changes in mRNA profiles induced by other stimuli. Unique signatures for anti-IgE antibody and IL-33 could be identified although the number of gene transcripts (6–30) that were unique to these two stimuli was very limited. There were no apparent unique profiles for IL-5, NGF, IL-2 or FMLP. Therefore, a potential tool for screening basophil phenotypes was limited to changes that could be induced by IL-3 (or no IL-3), IL-33 and anti-IgE Ab.
Highlights
Allergic diseases result from an immune response that is characterized by the presence and activities of IgE antibody
Relative to other polymorphonuclear leukocytes, basophils are relatively resistant to apoptosis [27,29], so changes that occur with or without IL-3 may represent initiation of apoptosis
It is unknown whether these changes can mask the effects of other non-IL-3 stimuli. This would be difficult to examine because only exposure in vivo could provide the necessary information and a controlled exposure in vivo is not likely to be done. With this concern in mind, the results suggest that of the stimuli examined, IL-3, or its lack, dominates the behavior of basophils and the behavior of the transcriptome
Summary
Allergic diseases result from an immune response that is characterized by the presence and activities of IgE antibody. The basophil is one of the target cells that has been shown in a variety of studies to participate in allergic diseases through its ability to bind IgE. Many studies have shown that there is significant variability in the ability of a subject’s basophils to respond through the IgE pathway. There is variability due to the relative presence of IgE and in particular, antigen-specific IgE. It is clear that there is considerable variability in the PLOS ONE | DOI:10.1371/journal.pone.0126435. It is clear that there is considerable variability in the PLOS ONE | DOI:10.1371/journal.pone.0126435 May 11, 2015
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