title: Toll-like receptor-induced reactivity and strongly potentiated IL-8 production in granulocytes mobilized for transfusion purposes.
abstract: Transfusion of granulocytes from granulocyte-colony stimulating factor (G-CSF)/dexamethasone (dexa)-treated donors can be beneficial for neutropenic recipients that are refractory to antimicrobial therapy. G-CSF/dexa treatment not only increases the number of circulating neutrophils but also affects their gene expression. Because of the intended transfusion of these granulocytes into patients who are severely ill, it is of importance to establish to what extent mobilization affects the cellular behavior of neutrophils. Here, we studied the effects of mobilization on Toll-like receptor (TLR)-mediated responses. Mobilized granulocytes displayed increased gene and protein expression of TLR2, TLR4, TLR5, and TLR8. Although mobilized granulocytes displayed normal priming of nicotinamide adenine dinucleotide phosphate oxidase activity and a slight increase in adhesion in response to TLR stimulation, these cells produced massive amounts of interleukin-8 (IL-8), in particular to TLR2 and TLR8 stimulation. The increase in IL-8 release occurred despite reduced IL-8 mRNA levels in the donor granulocytes after in vivo G-CSF/dexa treatment, indicating that the enhanced TLR-induced IL-8 production was largely determined by posttranscriptional regulation. In summary, granulocytes mobilized for transfusion purposes show enhanced TLR responsiveness in cytokine production, which is anticipated to be beneficial for the function of these cells on transfusion into patients.
authors.affiliation: Department of Blood Cell Research, Phagocyte Laboratory, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands. a.drewniak@sanquin.nl
authors.forename: Agata
authors.initials: A
authors.lastname: Drewniak
authors.forename: Anton T J
authors.initials: AT
authors.lastname: Tool
authors.forename: Judy
authors.initials: J
authors.lastname: Geissler
authors.forename: Robin
authors.initials: R
authors.lastname: van Bruggen
authors.forename: Timo K
authors.initials: TK
authors.lastname: van den Berg
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
mesh_terms: D001483:Base Sequence; D002448:Cell Adhesion; D018925:Chemokines / Q000097:blood; D017931:DNA Primers / Q000235:genetics; D003907:Dexamethasone / Q000008:administration & dosage; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006098:Granulocytes / Q000187:drug effects / Q000276:immunology* / Q000502:physiology / Q000637:transplantation*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D007937:Leukapheresis; D017708:Leukocyte Transfusion; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D011994:Recombinant Proteins; D051193:Toll-Like Receptors / Q000097:blood*
chemical_list: C508606:CXCL8 protein, human; D018925:Chemokines; D017931:DNA Primers; D016209:Interleukin-8; D012333:RNA, Messenger; D011994:Recombinant Proteins; D051193:Toll-Like Receptors; D016179:Granulocyte Colony-Stimulating Factor; D003907:Dexamethasone