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Eosinophils, but not neutrophils, exhibit an efficient DNA repair machinery and high nucleolar activity

From the Dipartimento di Scienze Biomediche, Sez. di Chimica Biologica, Università degli Studi di Modena e Reggio Emilia, Via Campi 287, 41100 Modena, Italy (RZ, ET, SF); Dipartimento di Scienze Biomediche, Sez. di Patologia Generale, Università degli Studi di Modena e Reggio Emilia, Via Campi 287, 41100 Modena, Italy (DQ)

Correspondence: Rossella Manfredini, MD, PhD, Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Università di Modena e Reggio Emilia, Via Campi 287, 41100 Modena, Italy. E-mail: manfredini.rossella{at}unimore.it

Background and Objectives: Traditionally eosinophils have been considered terminally differentiated cells that play a role in host protection against parasites. However, there is some evidence showing that eosinophils are, in fact, multifunctional leukocytes involved in inflammatory responses, as well as in tissue homeostasis. We characterized the transcriptome profile of human eosinophils, and, for the purpose of comparison, the transcriptome profile of neutrophils, monocytes and hematopoietic progenitor cells. Moreover, we studied the activation of selected cellular processes for which a significant differential expression was demonstrated.

Design and Methods: We profiled gene expression using Affymetrix GeneChips. DNA repair capacity was tested using the comet assay. Nucleoli and their activity were characterized by transmission electron microscopy analysis, silver staining of nucleolus regions (AgNOR) and RNA staining.

Results: Gene expression profiling showed that eosinophils appear hierarchically closer to monocytes than to neutrophils. Gene ontology mapping of differentially expressed genes revealed that eosinophils express categories very similar to those expressed by monocytes, related to DNA repair and nucleolar functions. Moreover, our data show that eosinophils and monocytes maintain the ability to repair both double and single strand DNA breaks, whereas neutrophils lack this capacity. Furthermore, eosinophils exibit nucleolar activity, which is lacking in neutrophils, but resembles that in monocytes.

Interpretation and Conclusions: The presence of large, active nucleoli in eosinophils, coupled to marked activity of DNA repair systems, suggests that eosinophils are not terminally differentiated cells. Indeed, their transcriptome profile and functional properties are more similar to those of non-terminally differentiated cells such as monocytes, rather than to neutrophils.

Key words: eosinophils, gene expression profile, DNA repair, nucleolar function, myeloid differentiation.