INTERLEUKIN-8 INDUCES RAPID MOBILIZATION OF HEMATOPOIETIC STEM-CELLS WITH RADIOPROTECTIVE CAPACITY AND LONG-TERM MYELOLYMPHOID REPOPULATINGABILITY

Interleukin-8 (IL-8) belongs to a family of chemoattractant cytokines involved in chemotaxis and activation of neutrophils. As in vivo admin istration of IL-8 induces granulocytosis and the release of immature w hite blood cells into the circulation, we assessed a possible mobilizi ng effect of IL-8 on myeloid progenitor cells, IL-8 was administered a t intraperitoneal doses ranging from 0.1 to 100 mu g per mouse to fema le Balb/C mice (aged 8 to 12 weeks; weight, 20 to 25 g). Animals were killed at time intervals ranging from 1 to 240 minutes after IL-8 admi nistration, and blood, bone marrow, and spleen cells were harvested. I njection of 30 mu g IL-8 resulted in an increment from 25 +/- 9 to 418 +/- 299 granulocyte-macrophage colony-forming units (CFU-GM) per mill iliter blood at 15 minutes after a single intraperitoneal injection. S ixty minutes after the injection of IL-8, the numbers of circulating C FU-GM per milliliter blood had almost returned to pretreatment values (82 +/- 39 CFU-GM per milliliter). A dose of 100 mu g IL-8 per animal did not result in a further increment in the number of circulating CFU -GM. Transplantation of 5 x 10(5) blood derived mononuclear cells (MNC ) obtained at 30 minutes after IL-8 injection (30 mu g) resulted in 69 % survival of lethally irradiated (8.5 Gy) recipients at 60 days versu s 22% for animals transplanted with an equal number of nonprimed blood -derived MNC. Transplantation of 1.5 x 10(6) MNC obtained from IL-8-tr eated donors resulted in 100% survival, Six months after transplantati on, female recipients of MNC derived from IL-8-treated male donors wer e killed, and chimerism was determined in bone marrow, spleen, and thy mus using a Y chromosome-specific probe and fluorescent in situ hybrid ization (FISH), The majority of bone marrow, spleen, and thymus cells (83% +/- 25%, 89% +/- 5%, and 64 +/- 28%, respectively) consisted of Y chromosome-positive cells, showing that the IL-8-mobilized cells had myelolymphoid repopulating ability. We conclude that IL-8 is a cytokin e that induces rapid mobilization of progenitor cells and pluripotent stem cells that are able to rescue lethally irradiated mice and that a re able to completely and permanently repopulate host hematopoietic ti ssues. (C) 1995 by The American Society of Hematology.