Interleukin-8: an autocrine/paracrine growth factor for human hematopoietic progenitors acting in synergy with colony stimulating factor-1 to promote monocyte-macrophage growth and differentiation

We previously reported that alteration of the function of heterotrimeric G(i2) proteins altered proliferation of murine macrophages in response to colony stimulating factor-1 (CSF-1), Here we show that a G(i2) agonist, C-X-C chemokine interleukin-8 (IL-8), regulates monocyte-macrophage growth and differentiation. In the absence of serum, IL-8 (10 ng/mL) synergized with CSF-1 to stimulate murine monocyte-macrophage proliferation, enhanced proliferation of purified human CD34(+) cells and increased the number and size of CSE-1-induced monocyte-macrophage colonies formed by purified CD34(+) cells in semisolid medium. Next, as both CD34(+) cells and monocyte-macrophages can produce IL-8, we used an anti-human IL-8 antibody to block an eventual activation of IL-8 receptors by autocrine IL-8, Preincubation with anti-human IL-8 antibody (20-40 mu g/mL) inhibited the proliferation as well as the monocyte-macrophage colony clonogenicity of purified human CD34(+) cells. Hence, in addition to being a powerful neutrophil chemoattractant, IL-8 also acts as an autocrine/paracrine growth factor for human hematopoietic progenitors, promoting the growth and differentiation of cells of monocytic lineage, (C) 1999 International Society for Experimental Hematology. Published by Elsevier Science Inc.