Hematopoietic stem cell mobilization with G-CSF induces innate inflammation yet suppresses adaptive immune gene expression as revealed by microarray analysis.

Abstract:

OBJECTIVE:Granulocyte colony-stimulating factor (G-CSF) is used to boost granulocyte counts in immunocompromised patients, but its effects on the immune system may be counterproductive. We tested the hypothesis that G-CSF-mobilized peripheral blood stem cell (PBSC) products are immunologically downregulated based on gene microarray analysis. METHODS:Ten peripheral blood samples from normal donors for allogeneic PBSC transplantation were obtained before and after administration of G-CSF and tested on Affymetrix Human U133 Plus 2.0 GeneChip microarrays and by flow cytometry. Significant changes in gene expression after G-CSF were reported by controlling the false discovery rate at 5%. The quantitative real-time polymerase chain reaction method was used to validate expression of representative genes. RESULTS:All immune cells measured, including neutrophils, monocytes, lymphocytes, and dendritic cells, were significantly increased after G-CSF. In terms of gene expression, inflammatory and neutrophil activation pathways were upregulated after G-CSF. However, adaptive immune-related gene expression, such as antigen presentation, co-stimulation, T-cell activation and cytolytic effector responses, were downregulated. CONCLUSION:Despite significant increases in lymphocytes and antigen-presenting cells, G-CSF-mobilized PBSC allografts exhibit a suppressive adaptive immune-related gene-expression profile. However, innate and inflammatory responses are elevated. Our data provides an explanation for the potentially immunosuppressive effects observed after G-CSF administration.

journal_name

Exp Hematol

journal_title

Experimental hematology

authors

Buzzeo MP,Yang J,Casella G,Reddy V

doi

10.1016/j.exphem.2007.06.001

subject

Has Abstract

pub_date

2007-09-01 00:00:00

pages

1456-65

issue

9

eissn

0301-472X

issn

1873-2399

pii

S0301-472X(07)00352-9

journal_volume

35

pub_type

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