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


CONCLUSIONS
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.
Buzzeo
Matthew P
MP
Department of Medicine, Division of Hematology/Oncology, University of Florida, Gainesville, Florida 32610-0277, USA.
Yang
Jie
J
Casella
George
G
Reddy
Vijay
V
D051940:B7-2 Antigen / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000502:physiology*; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology*; D046228:Microarray Analysis; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D051940:B7-2 Antigen; C468140:CD28-binding protein, human; C497964:CD86 protein, human; D002352:Carrier Proteins; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor