Interleukin-8 and Other Agonists of Gi2 Proteins: Autocrine Paracrine Growth Factors for Human Hematopoietic Progenitors Acting in Synergy with Colony Stimulating Factors

Abstract

We have reviewed the current knowledge on CXC chemokine interleukin-8 (IL-8) and human hematopoiesis, and more generally on agonists of heterotrimeric Gi2 proteins as regulators of human hematopoiesis. It appears that low doses of IL-8, a Gi2-agonist produced in an autocrine fashion by normal hematopoietic progenitors, mature blood cells and leukemic cells, promotes cell survival or/and proliferation in response to hematopoietic cytokines. More importantly, inactivation of the IL-8/Gi2 pathways inhibits CD34+ cell proliferation and colony formation. Similar positive effects on hematopoiesis of other, physiological or pathological, agonists of Gi2 proteins are discussed, as well as the molecular pathways involved and the consequences of activation of other G proteins (Gq, G16) by IL-8 and other Gi2-agonists.

Key Words:

• IL-8
• Gi2 proteins
• GCRs (C protein-coupled receptors)
• human hematopoietic cells
• Colony Stimulating Factors (CSFs)