title: Pasteurella multocida toxin activates human monocyte-derived and murine bone marrow-derived dendritic cells in vitro but suppresses antibody production in vivo.
abstract: Pasteurella multocida toxin (PMT) is a potent mitogen for fibroblasts and osteoblastic cells. PMT activates phospholipase C-beta through G(q)alpha, and the activation of this pathway is responsible for its mitogenic activity. Here, we investigated the effects of PMT on human monocyte-derived dendritic cells (MDDC) in vitro and show a novel activity for PMT. In this regard, PMT activates MDDC to mature in a dose-dependent manner through the activation of phospholipase C and subsequent mobilization of calcium. This activation was accompanied by enhanced stimulation of naive alloreactive T cells and dominant inhibition of interleukin-12 production in the presence of saturating concentrations of lipopolysaccharide. Surprisingly, although PMT mimics the activating effects of cholera toxin on human MDDC and mouse bone marrow-derived dendritic cells, we found that PMT is not a mucosal adjuvant and that it suppresses the adjuvant effects of cholera toxin in mice. Together, these results indicate discordant effects for PMT in vitro compared to those in vivo.
authors.affiliation: Division of Vaccine Research, Institute of Human Virology, University of Maryland Baltimore, 725 W. Lombard St., Baltimore, MD 21201, USA. lewisg@umbi.umd.edu
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Bagley
authors.forename: Sayed F
authors.initials: SF
authors.lastname: Abdelwahab
authors.forename: Robert G
authors.initials: RG
authors.lastname: Tuskan
authors.forename: George K
authors.initials: GK
authors.lastname: Lewis
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001426:Bacterial Proteins / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002772:Cholera Toxin / Q000037:antagonists & inhibitors; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D018664:Interleukin-12 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology; D010047:Ovalbumin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D019284:Thapsigargin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D016207:Cytokines; C062258:Pasteurella multocida toxin; D018664:Interleukin-12; D000001:Calcimycin; D019284:Thapsigargin; D010047:Ovalbumin; D002772:Cholera Toxin; D010738:Type C Phospholipases; D002118:Calcium