title: Class 3 semaphorins induce F-actin reorganization in human dendritic cells: Role in cell migration.
abstract: Class 3 semaphorins (Semas) are soluble proteins that are well recognized for their role in guiding axonal migration during neuronal development. In the immune system, Sema3A has been shown to influence murine dendritic cell (DC) migration by signaling through a neuropilin (NRP)-1/plexin-A1 coreceptor axis. Potential roles for class 3 Semas in human DCs have yet to be described. We tested the hypothesis that Sema3A, -3C, and -3F, each with a unique NRP-1 and/or NRP-2 binding specificity, influence human DC migration. In this report, we find that although NRP-1 and NRP-2 are expressed in human immature DCs (imDCs), NRP-2 expression increases as cells mature further, whereas expression of NRP-1 declines dramatically. Elevated levels of RNA encoding plexin-A1 and -A3 are present in both imDCs and mature DC (mDCs), supporting the relevance of Sema/NRP/plexin signaling pathways in these cells. Sema3A, -3C, and -3F bind to human DCs, with Sema3F binding predominantly through NRP-2. The binding of these Semas leads to reorganization of actin filaments at the plasma membrane and increased transwell migration in the absence or presence of chemokine CCL19. Microfluidic chamber assays failed to demonstrate consistent changes in speed of Sema3C-treated DCs, suggesting increased cell deformability as a possible explanation for enhanced transwell migration. Although monocytes express RNA encoding Sema3A, -3C, and -3F, only RNA encoding Sema3C increases robustly during DC differentiation. These data suggest that Sema3A, -3C, and -3F, likely with coreceptors NRP-1, NRP-2, and plexin-A1 and/or -A3, promote migration and possibly other activities of human DCs during innate and adaptive immune responses.
authors.affiliation: Institute of Human Virology, University of Maryland Medical Center, Baltimore, Maryland, USA.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Curreli
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Bin Sheng
authors.initials: BS
authors.lastname: Wong
authors.affiliation: Institute of Human Virology, University of Maryland Medical Center, Baltimore, Maryland, USA.|Department of Microbiology and Immunology, University of Maryland Medical Center, Baltimore, Maryland, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Latinovic
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Konstantopoulos
authors.affiliation: Institute of Human Virology, University of Maryland Medical Center, Baltimore, Maryland, USA; nstamatos@ihv.umaryland.edu.|Department of Medicine, University of Maryland Medical Center, Baltimore, Maryland, USA; and.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Stamatos
mesh_terms: D008841:Actin Cytoskeleton / Q000648:ultrastructure*; D000199:Actins / Q000378:metabolism*; D056704:Adaptive Immunity; D002454:Cell Differentiation; D002478:Cells, Cultured; D054415:Chemokine CCL19 / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects* / Q000502:physiology; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D003713:Dendritic Cells / Q000187:drug effects* / Q000648:ultrastructure; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D046210:Microfluidic Analytical Techniques; D009419:Nerve Tissue Proteins / Q000378:metabolism; D039942:Neuropilin-1 / Q000378:metabolism; D039943:Neuropilin-2 / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000199:Actins; C515460:CCL19 protein, human; D054415:Chemokine CCL19; D009419:Nerve Tissue Proteins; D039943:Neuropilin-2; C492116:PLXNA1 protein, human; C515995:PLXNA2 protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D039961:Semaphorins; C581308:neuropilin-2, human; D039942:Neuropilin-1
keywords: chemotaxis; neuropilin-1 and -2; plexins; polysialic acid