[Chemokines and the regulation of hematopoiesis].

Abstract

Chemokines are a large family of cytokines that act not only as immune and inflammatory regulators but also as regulators of hematopoiesis. Two major subfamilies of chemokines are distinguished on the basis of whether the first two cysteines are separated by a single residue (CXC) or three residues (CX3C) or they are adjacent (CC) or there is a single C. The Macrophage Inflammatory Protein 1 alpha (MIP-1 alpha), which belongs to CC family is a powerful inhibitor of hematopoisis in vitro and in vivo. The sub-family CXC comprises two main groups. The first sub-group includes the ELR chemokines, in which interleukin-8 (IL-8) is the most prototypic and possesses suppressive activities on hematopoiesis. Platelet Factor 4 (PF4) belongs to the sub-group of non-ELR CXC chemokines. PF4 acts as an inhibitor of hematopoiesis, particularly of the megakaryocytopoiesis. Recently, it has been shown that a peptide of PF4, 34-58 which does not contain the site of heparin binding, is able to inhibit the growth of hematopoietic progenitors in vitro, providing evidence for a model of heparin dependent and independent pathways of PF4 action on hematopoiesis. PF4 can reduce the chimiosensitivity of hematopoietic cells in mice treated by the cytotoxic drug 5-Fluorouracyl, suggesting a potential clinical application of PF4 in cancer therapy.