title: Neurotrophins modulate monocyte chemotaxis without affecting macrophage function.
abstract: Neurotrophins nerve growth factor (NGF), brain-derived growth factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) and their high-affinity tyrosine protein kinase receptor (Trk) family, TrkA, TrkB, TrkC, and low-affinity p75(NTR) receptor, are key molecules implicated in the development of the central nervous system. Increasing evidence suggests that they also have physiological and pathological roles outside the nervous system. In this study we examined the expression of neurotrophins and their receptors in human activated macrophages and to what extent neurotrophins themselves modulate macrophage activation, in a model of primary adult monocyte-derived macrophage. Our data indicate that macrophages express neurotrophin and neurotrophin receptor genes differentially, and respond to cell stimulation by specific inductions. Neurotrophins did not modify the antigen-presenting capacities of macrophages or their production of proinflammatory cytokines, but somehow skewed their activation phenotype. In contrast, NGF clearly increased CXCR-4 expression in macrophage and their chemotactic response to low CXCL-12 concentration. The differential effect of specific macrophage stimuli on neurotrophin expression, in particular NGF and NT-3, and the specific enhancement of CXCR-4 expression suggest that neurotrophins might participate in tissue-healing mechanisms that should be investigated further in vivo.
authors.affiliation: CEA, DSV, iMETI, SIV, UMR E-01 Université Paris Sud, IFR13 Institut Paris Sud Cytokines, Service d'Immuno-Virologie, Fontenay-aux Roses, France.
authors.forename: B
authors.initials: B
authors.lastname: Samah
authors.forename: F
authors.initials: F
authors.lastname: Porcheray
authors.forename: G
authors.initials: G
authors.lastname: Gras
mesh_terms: D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007959:Lymphocyte Culture Test, Mixed; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D020932:Nerve Growth Factor / Q000276:immunology; D009414:Nerve Growth Factors / Q000276:immunology* / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D009414:Nerve Growth Factors; D017475:Receptors, Nerve Growth Factor; D020932:Nerve Growth Factor