[Substance P as a regulatory peptide of hematopoiesis and blood cell functions]

Abstract

SP is an undecapeptide that belongs to the family of related neurokinins termed tachykinins. SP is one of the mediators responsible for the neural-immune/hematopoietic cross-talk. It is released from the nerve fibers of the autonomic and enteric nervous systems in lymphoid organs and is also produced by the resident, stromal or hematopoietic cells. SP stimulates the production of hematopoietic cytokines (e.g. IL-1, IL-3, IL-6, SCF, GM-CSF) by bone marrow stromal cells. It enhances the proliferation of bone marrow progenitors, both directly by binding to progenitor's receptors and indirectly by interacting with marrow stromal cells. SP can also modulate immune and hematopoietic functions like phagocytosis, immunoglobulin production, lymphocyte proliferation and platelet aggregation. SP fragments derived from endopeptidase activity could also exert immune and hematopoietic regulation. The biological effects of SP are mediated through interactions with certain G protein-coupled receptors: the neurokinin (NK) receptors. Different studies have shown that NK receptors are localized on immuno-competent cells, including monocytes/macrophages, neutrophils, mast cells, dendritic cells and T or B lymphocytes, bone marrow stromal cells and hematopoietic progenitors. The disturbance of the neural-hematopoietic-immune axis may be implicated in hematological malignancies. SP seems to be important in the neoplastic transformation of bone marrow, leading to the development of acute leukaemia in children; myelofibrosis and also metastases to bone marrow of solid tumors in early stages of these diseases.