It has recently been established that neutrophils, the most abundant leukocytes, are capable of changes in gene expression during inflammatory responses. However, changes in the transcriptome as the neutrophil leaves the bone marrow have yet to be described. We hypothesized that neutrophils are transcriptionally active cells that alter their gene expression profiles as they migrate into the vasculature and then into inflamed tissues. Our goal was to provide an overview of how the neutrophil's transcriptome changes as they migrate through different compartments using microarray and bio-informatic approaches. Our study demonstrates that neutrophils are highly plastic cells where normal environmental cues result in a site-specific neutrophil transcriptome. We demonstrate that neutrophil genes undergo one of four distinct expression change patterns as they move from bone marrow through the circulation to sites of inflammation: (i) continuously increasing; (ii) continuously decreasing; (iii) a down-up-down; and (iv) an up-down-up pattern. Additionally, we demonstrate that the neutrophil migration signaling network and the balance between anti-apoptotic and pro-apoptotic signaling are two of the main regulatory mechanisms that change as the neutrophil transits through compartments.
Bibliographical noteFunding Information:
This work was funded by an operating grant from The Canadian Institutes of Health Research (CIHR, Ottawa, ON, Canada) to MG. FL is supported by CIHR Training Fellowship, TGF-53877 and the Harron scholarship (Faculty of Dentistry, University of Toronto). The authors give special thanks to Dionne White from The Flow Cytometric Facility of the Immunology Department, Faculty of Medicine of University of Toronto for assistance with flow cytometric analysis, also to Guillermo Casallo and Pingzhao Hu of the Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Canada, for assistance with microarray analysis and statistical analysis respectively.
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