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Stefan Dichmann

Publications and source records attributed to Stefan Dichmann.

7 recordsLinked to original sources
PubMed2002

The influence of lysophosphatidic acid on the functions of human dendritic cells.

Lysophosphatidic acid (LPA) is a bioactive lipid mediator which is generated by secretory phospholipase A(2). In this study, we studied the biological activity of LPA on human dendritic cells (DCs), which are specialized APCs characterized by their ability to migrate into target sites and secondary lymphoid organs to process Ags and activate naive T cells. We show that immature and mature DCs express the mRNA for different LPA receptors such as endothelial differentiation gene (EDG)-2, EDG-4, and EDG-7. In immature DCs, LPA stimulated pertussis toxin-sensitive Ca(2+) increase, actin polymerization, and chemotaxis. During the maturation process, DCs lost their ability to respond toward LPA with Ca(2+) transients, actin polymerization, and chemotaxis. However, LPA inhibited in a pertussis toxin-insensitive manner the secretion of IL-12 and TNFalpha as well as enhanced secretion of IL-10 from mature DCs. Moreover, LPA did not affect the endocytic or phagocytic capacities and the surface phenotype of DCs, although it increased the allostimulatory function of mature DC and inhibited their capacity to induce Th1 differentiation. In summary, our study implicates that LPA might regulate the trafficking, cytokine production, and T cell-activating functions of DCs.

Actins↗
PubMed2002

Nucleotides induce chemotaxis and actin polymerization in immature but not mature human dendritic cells via activation of pertussis toxin-sensitive P2y receptors.

Dendritic cells (DCs) are considered the principal initiators of immune response because of their ability to migrate into peripheral tissues and lymphoid organs, process antigens, and activate naive T cells. There is evidence that extracellular nucleotides regulate certain functions of DCs via G-protein-coupled P2Y receptors (P2YR) and ion-channel-gated P2X receptors (P2XR). Here we investigated the chemotactic activity and analyzed the migration-associated intracellular signaling events such as actin reorganization and Ca(++) transients induced by common P2R agonists such as adenosine 5'-triphosphate (ATP) and 2-methylthioadenosine triphosphate, the P2YR agonists UTP and adenosine 5'-diphosphate (ADP), or the P2XR agonists alphabeta-methylenadenosine-5'-triphosphate and 2',3'-(4-benzoyl)benzoyl-ATP. The common P2R agonists and the selective P2YR agonists turned out to be potent chemotactic stimuli for immature DCs, but not for mature DCs. In contrast, P2XR agonists had only marginal chemotactic activity in both DC types. Chemotaxis was paralleled by a rise in the intracellular Ca(++) concentration and by actin polymerization. Studies with pertussis toxin implicated that intracellular signaling events such as actin polymerization, mobilization of intracellular Ca(++), and migration induced by nucleotides was mediated via G(i/o) protein-coupled P2YR. Moreover, functional studies revealed selective down-regulation of this G(i/o) protein-coupled chemotactic P2YR responsiveness during maturation, although immature and mature DCs expressed similar amounts of mRNA for the P2R subtypes (P2Y(2)R, P2Y(4)R, P2Y(5)R, P2Y(7)R, P2Y(11)R and P2X(1)R, P2X(4)R, P2X(7)R), and no major differences in respect to the mRNA expression of these receptors could be observed by semiquantitative reverse transcription and polymerase chain reaction (RT-PCR). In summary, our data describe a differential chemotactic response of immature and mature DCs to nucleotides, and lend further support to the hypothesis that P2R are a novel class of immunomodulatory plasma membrane receptors suitable for pharmacological intervention.

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PubMed2002

[Ocular syphilis].

BACKGROUND: Syphilis has distinctly increased in the last decades. It is necessary to know the different eye changes in syphilis. PATIENTS: In four patients, between 34 and 71 years of age, typical as well as unusual syphilitic eye changes were found. In three patients diagnosis was made due to the inflammatory eye changes. RESULTS: An iritis was found in two patients (62 and 34 years old). In addition, the 62-year-old patient showed the unusual fundus picture of both vasculitis and neuroretinitis, with macular exudates and swelling of the optic disk. A venous occlusion, a rare sign in syphilis, was diagnosed in a 55-year-old patient. A 71-year-old patient revealed the characteristic finding of a placoid chorioretinitis. All four patients showed a swelling of the optic disk. CONCLUSION: Syphilis should be suspected even in older patients with an uncertain origin of uveitis, optic nerve disease, pupillary changes, or eye motility disturbances giving rise to carry out serologic tests in patients with the suspected diagnosis.

Adult↗
PubMed2002

Expression and function of histamine receptors in human monocyte-derived dendritic cells.

BACKGROUND: Histamine is a well-known mediator eliciting different responses in immune and nonimmune cells, but its role in modulating dendritic cell (DC) functions has been marginally investigated. OBJECTIVE: The purpose of this investigation was to analyze whether human monocyte-derived DCs express functional histamine receptors according to their maturation stage. METHODS: DCs were derived from monocytes and used as immature or LPS-differentiated cells. DCs were tested for histamine receptor expression, chemotaxis, cytokine release, and the capacity to induce T-cell differentiation in response to specific histamine receptor agonists. RESULTS: Immature and mature DCs expressed the mRNA for H1, H2, and H3 histamine receptors. Histamine induced intracellular Ca2+ transients, actin polymerization, and chemotaxis in immature DCs. Maturation of DCs resulted in the loss of these responses. In maturing DCs, however, histamine dose-dependently enhanced intracellular cAMP levels and stimulated IL-10 secretion while inhibiting production of IL-12. As a consequence, histamine might contribute to the impairment of generation of allogeneic type 1 responses via maturing DCs. Specific histamine receptor agonists or antagonists revealed that Ca2+ transients, actin polymerization, and chemotaxis of immature DCs were due to stimulation of H1 and H3 subtypes. Modulation of IL-12 and IL-10 secretion by histamine involved the H2 and H3 receptors exclusively. CONCLUSIONS: Our study suggests that histamine has important biological effects on DC activities, opening the possibility that histamine released during inflammatory or immune responses could regulate DC functions and ultimately favor type 2 lymphocyte-dominated immunity.

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PubMed2002

Sphingosine 1-phosphate induces chemotaxis of immature and modulates cytokine-release in mature human dendritic cells for emergence of Th2 immune responses.

Sphingosine 1-phosphate (S1P) is a potent extracellular lysolipid phosphoric acid mediator that is released after IgE-stimulation of mast cells. Here we investigated the biological activity and intracellular signaling of S1P on human dendritic cells (DC), which are specialized antigen presenting cells with the ability to migrate into peripheral tissues and lymph nodes, as well as control the activation of naive T cells. We show that immature and mature DC express the mRNA for different S1P receptors, such as endothelial differentiation gene (EDG)-1, EDG-3, EDG-5, and EDG-6. In immature DC, S1P stimulated pertussis toxin-sensitive Ca2+ increase actin-polymerization and chemotaxis. These responses were lost by DC matured with lipopolysaccharide. In maturing DC, however, S1P inhibited the secretion of tumor necrosis factor alpha and interleukin (IL)-12, whereas it enhanced secretion of IL-10. As a consequence, mature DC exposed to S1P showed a reduced and increased capacity to generate allogeneic Th1 and Th2 responses, respectively. In summary, our study implicates that S1P might regulate the trafficking of DC and ultimately favor Th2 lymphocyte-dominated immunity.

Actins↗
PubMedDate not supplied

Tumor necrosis factor alpha induces upregulation of CXC-chemokine receptor type II expression and magnifies the proliferative activity of CXC-chemokines in human melanocytes.

The CXC-chemokines Groalpha and interleukin-8 (IL-8) are ligands for two different G protein-coupled receptors, named CXC-chemokine receptor I & II (CXCRI & II). Both cytokines are potent growth factors for human melanoma cells, with only limited proliferative activity towards normal melanocytes. Here we analysed the influence of various cytokines on the expression of CXCRI & II and the CXC-chemokine-induced proliferation in human melanocytes. Flow cytometric studies revealed no protein expression of CXCRI and low protein expression of CXCRII at the cell surface of normal melanocytes. Tumor necrosis factor alpha (TNFalpha) enhanced the mRNA and protein expression of CXCRII, but did not influence expression of CXCRI. A consequence of TNFalpha-pretreatment of human melanocytes was a significant enhancement of the proliferative activity of IL-8 and Groalpha. This study implicates that TNFalpha magnifies the biological activity of CXC-chemokines in melanocytes by induction of CXCRII expression.

Cell Division↗