Interleukine-8 acts as a strong peripheral blood granulocyte-recruiting agent rather than as a hematopoietic progenitor cell-mobilizing factor.
Intravenous infusion of Interleukine-8 has been shown to lead to a rapid mobilization of hematopoietic cells in mice and rhesus monkeys. We report in this study that the IL-8-mediated mobilizing effect results in low levels of circulating CD34+ cells, whereas a rapid and strong recruitment of mature granulocytes occurs. This would be of great interest for harvesting large numbers of functional granulocytes to fight infection in immunodepressed patients. We performed a kinetic study of the mobilization in a nonhuman primate model (Papio ursinus), mobilized with a single or double infusion of IL-8 with a dose range of 30-50 microg/kg of body weight. Blood was sampled every 15 min after the IL-8 infusion, and IL-8 plasma levels, complete blood counts, differential WBCC, colony-forming unit assays, and CD34+ cell evaluation assays were performed. At the same time, leukapheresis was performed on the anesthetized animal to collect either hematopoietic stem and progenitor cells (HSPC) or peripheral blood granulocytes (PBG) according to different collection settings. IL-8 induced a rapid increase of PBG (7-12-fold the basal values). The HSPC leukapheresis concentrate showed poor ex vivo expansion abilities. IL-8-mobilized peripheral blood polymorphonuclear cells showed normal oxidative, chemotactic, phagocytic, and adherence abilities. We suggest that IL-8-induced neutrophilia could be used as an allogeneic source of granulocytes for transfusion in neutropenic patients or in granulocyte dysfunction.
Vetillard
J
J
Institut de Protection et de Sûreté Nucléaire, Département de Protection de la santé de l'Homme et de Dosimétrie, Centre d'Etude Nucléaire de Fontenay-Aux-Roses, France.
Drouet
M
M
Neildez-Nguyen
T M
TM
Mestries
J C
JC
Mathieu
J
J
Thierry
D
D
Herodin
F
F
D000818:Animals; D018952:Antigens, CD34; D001772:Blood Cell Count; D006098:Granulocytes / Q000187:drug effects* / Q000473:pathology*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology*; D017708:Leukocyte Transfusion; D008297:Male; D051379:Mice; D010215:Papio
D018952:Antigens, CD34; D016209:Interleukin-8