Neuropeptide control of bone marrow neutrophil production. A key axis for neuroimmunomodulation.
Nerve fibers project into the bone marrow and terminate in association with stromal cells. Nerve terminals are also associated with antigen-processing and -presenting cells throughout the body and have been shown to be important in leukocyte trafficking and wound healing as well as hemopoiesis. Here we show that neuropeptide input to the bone marrow is vital to normal granulopoiesis and that deletion of the neuropeptides, substance P, and calcitonin gene-related peptide (CGRP), with the neurotoxin, capsaicin, abrogates normal blood cell production. Norepinephrine, neurokinins a and 2, and vasoactive intestinal peptide all have inhibitory effects on in vitro CFU-GM colony formation. Substance P, neurokinin 1, nerve growth factor, and CGRP have stimulatory effects on CFU-GM. Furthermore, in vitro experiments show that, apart from CGRP, all the neuroactive substances we tested operate through effects on accessory cells, stimulating the release of regulatory molecules that have a direct effect on purified CFU-GM.
Neuroscience and Cell Biology Research Group, Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology, P.O. Box 88, Manchester M60 1QD, United Kingdom.
C S
CS
Broome
J A
JA
Miyan
D000818:Animals; D001853:Bone Marrow / Q000502:physiology*; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000494:pharmacology / Q000502:physiology*; D015213:Neuroimmunomodulation; D009504:Neutrophils / Q000166:cytology / Q000502:physiology*
D009419:Nerve Tissue Proteins