Medical Library

Dendritic cell expression of the Notch ligand jagged2 is not essential for Th2 response induction in vivo.

We have addressed the hypothesis that Notch ligands play a decisive role in determining the ability of antigen-presenting cells to influence T cell polarization. Dendritic cells displayed distinct expression profiles of Delta and Jagged ligands for Notch when exposed to biologically relevant pathogen preparations associated with Th1 or Th2 responses. Expression of delta4 was increased, and jagged2 decreased, after dendritic cell exposure to the Th1-promoting bacterium Propionibacterium acnes. In contrast, soluble egg antigen (SEA) from the parasitic helminth Schistosoma mansoni, a potent Th2 inducer, failed to significantly alter dendritic cell expression of any of the Notch ligands measured. Irrespective of this, jagged2-deficient dendritic cells were severely impaired in their ability to instruct Th2 polarization of naive T cells in vitro. However, the ability of SEA-pulsed jagged2-deficient dendritic cells to induce a Th2 response in vivo was unimpaired relative to jagged2-sufficient dendritic cells. Further, jagged2-deficient dendritic cells activated by P. acnes exhibited no evidence of enhanced (or impaired) Th1 induction in vivo. These data suggest that, although involved in Th2 direction in vitro, jagged2 is not fundamentally required for Th2 induction by SEA-activated dendritic cells in vivo.

Worsley AG, Leibundgut-Landmann S, Slack E, Phng LK, Gerhardt H, Sousa CR, Macdonald AS.

Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.

Dendritic cells in colonic patches and iliac lymph nodes are essential in mucosal IgA induction following intrarectal administration via CCR7 interaction.

This study examined dendritic cells (DC) following intrarectal (IR) vaccination with the mucosal adjuvant cholera toxin (CT). Three rounds of IR vaccination with ovalbumin (OVA) and CT resulted in brisk levels of systemic and mucosal Ig responses. Immunohistochemical studies revealed that CD11c(+ )MHC class II(+) cells accumulated primarily in the colonic patches (CP) and lamina propria of the large intestine (LI-LP), iliac LN (ILN) and MLN following IR vaccination with CT. Adoptively transferred CFSE-labeled OVA-specific CD4(+) T cells proliferated significantly, secreting predominantly Th1-type cytokines in the CP (48 h after IR vaccination with CT) and Th2-type cytokines in the ILN (96 h after IR vaccination with CT). Following three IR vaccinations, CP-null mice that were generated by in utero treatment with anti-IL-7R Ab showed reduced levels of serum IgG and fecal IgA antibodies, suggesting a crucial role for CP in the initiation of systemic and mucosal immune responses. Of most interest, IR vaccination reduced IgA levels in fecal extracts significantly more in the CCR7(-/-) mice than in the wild-type mice. These results indicate that IR vaccination primarily mobilizes CD11c(+) cells in the CP and ILN to induce optimal mucosal immune responses by CCR7 interaction.

Lee AY, Chang SY, Kim JI, Cha HR, Jang MH, Yamamoto M, Kweon MN.

Mucosal Immunology Section, International Vaccine Institute, Seoul, Korea.

Coxiella burnetii, the agent of Q fever, stimulates an atypical M2 activation program in human macrophages.

Coxiella burnetii is an obligate intracellular bacterium, responsible for Q fever, which survives in macrophages by interfering with their microbicidal competence. As functional polarization of macrophages is critical for their microbicidal activity, we studied the activation program of monocyte-derived macrophages (MDM) stimulated with C. burnetii. This program was markedly distinct from that induced by lipopolysaccharides (LPS), a canonical inducer of M1 polarization. Indeed, C. burnetii up-regulated the expression of genes associated with M2 polarization, including TGF-beta1, IL-1 receptor antagonist (IL-1ra), CCL18, the mannose receptor and arginase-1, and only up-regulated the expression of two genes associated with M1 polarization, namely IL-6 and CXCL8. In contrast, C. burnetii down-regulated the expression of genes associated with M1 polarization such as TNF, CD80, CCR7 and TLR-2. Functional analyses showed that C. burnetii-stimulated MDM produced high levels of TGF-beta1 and CCL18, and expressed the mannose receptor and arginase-1, the latter being associated with the prevention of nitric oxide production by MDM. Finally, C. burnetii induced the release of IL-6 and CXCL8 at a lower level than LPS-stimulated MDM. Our results suggest that C. burnetii stimulated an atypical M2 activation program that may account for the persistence of C. burnetii in macrophages.Supporting Information for this article is available at http://www.wiley-vch.de/contents/jc_2040/2008/37917_s.pdf.

Benoit M, Barbarat B, Bernard A, Olive D, Mege JL.

Unité des Rickettsies, CNRS UMR 6020, IFR 48, Université de la Méditerranée, Faculté de Médecine, Marseille, France.

Open-Pore Biodegradable Foams Prepared via Gas Foaming and Microparticulate Templating.

Open-pore biodegradable foams with controlled porous architectures were prepared by combining gas foaming and microparticulate templating. Microparticulate composites of poly(epsilon-caprolactone) (PCL) and micrometric sodium chloride particles (NaCl), in concentrations ranging from 70/30 to 20/80 wt.-% of PCL/NaCl were melt-mixed and gas-foamed using carbon dioxide as physical blowing agent. The effects of microparticle concentration, foaming temperature, and pressure drop rate on foam microstructure were surveyed and related to the viscoelastic properties of the polymer/microparticle composite melt. Results showed that foams with open-pore networks can be obtained and that porosity, pore size, and interconnectivity may be finely modulated by optimizing the processing parameters. Furthermore, the ability to obtain a spatial gradient of porosity embossed within the three-dimensional polymer structure was exploited by using a heterogeneous microparticle filling. Results indicated that by foaming composites with microparticle concentration gradients, it was also possible to control the porosity and pore-size spatial distribution of the open-pore PCL foams.

Salerno A, Iannace S, Netti PA.

Interdisciplinary Research Centre on Biomaterials (CRIB) and Italian Institute of Technology (IIT), Piazzale Tecchio 80, 80125 Naples, Italy.

Plasma Surface Modification of Chitosan Membranes: Characterization and Preliminary Cell Response Studies.

Surface modification of biomaterials is a way to tailor cell responses whilst retaining the bulk properties. In this work, chitosan membranes were prepared by solvent casting and treated with nitrogen or argon plasma at 20 W for 10-40 min. AFM indicated an increase in the surface roughness as a result of the ongoing etching process. XPS and contact angle measurements showed different surface elemental compositions and higher surface free energy. The MTS test and direct contact assays with an L929 fibroblast cell line indicated that the plasma treatment improved the cell adhesion and proliferation. Overall, the results demonstrated that such plasma treatments could significantly improve the biocompatibility of chitosan membranes and thus improve their potential in wound dressings and tissue engineering applications.

Silva SS, Luna SM, Gomes ME, Benesch J, Pashkuleva I, Mano JF, Reis RL.

3B\’s Research Group - Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, Campus de Gualtar, 4710‐057 Braga, Portugal.

Biodegradable Nanoparticles of Partially Methylated Fungal Poly(beta-L-malic acid) as a Novel Protein Delivery Carrier.

The preparation of nanoparticles from 75% methylated poly(beta-L-malic acid) is described. Their degradation in aqueous environments was examined and the influence of pH and lipase on the rate of hydrolysis was evaluated. Six proteins were used to estimate the loading efficiency of the nanoparticles. The amount of protein retained in the nanoparticles was found to depend on the acid/basic character of the protein. Protein release from the loaded nanoparticles upon incubation in water under physiological conditions encompassed polymer hydrolysis and happened steadily within 3-10 d. The activity loss of entrapped alpha-chymotrypsin caused by loading and releasing depended on the method used for loading.

Portilla-Arias JA, García-Alvarez M, Galbis JA, Muñoz-Guerra S.

Departament d\’Enginyeria Química, Universitat Politècnica de Catalunya, ETSEIB, Diagonal 647, 08028 Barcelona, Spain.

Chemical Conjugation of Linear and Cyclic RGD Moieties to a Recombinant Elastin-Mimetic Polypeptide - A Versatile Approach towards Bioactive Protein Hydrogels.

An elastin-mimetic polypeptide, (EMM)(7), with the amino-acid sequence GRDPSS [VPGVG VPGKG VPGVG VPGVG VPGEG VPGIG](7) was used for chemical conjugation of various integrin ligands (RGD peptides) to prepare bioactive hydrogels. The chemical approach involved (1) chemical protection of lysine residues with Fmoc or Boc groups, (2) chemical ligation of a protected linear or cyclic RGD ligand, with or without a hexanoic-acid spacer to the glutamic acid residue, (3) deprotection of the lysine functionalities and the RGD moieties and (4) cross-linking to form a bioactive hydrogel. (1)H NMR spectroscopy was used to quantify the multiple steps in the reaction. The chemical protection was found to be between 65 and 93% for Fmoc and Boc, respectively. The ligands studied included linear RGD cell-binding [H–FGRGDS–OH (1-l-RGD), H–Ahx–FGRGDS–OH (2-Ahx–FGRGDS) and a cyclic –H(2)N–(CH(2))(6)COHN–cyclo(–RGDfK–) (H–Ahx–c(–RGDfK–)) peptide also with a hexanoic-acid spacer. Cell adhesion with mouse osteoblast cells was dependent on the ligand type, ligand density and the use of a spacer.

Kaufmann D, Fiedler A, Junger A, Auernheimer J, Kessler H, Weberskirch R.

TU München, Department Chemie, WACKER Lehrstuhl für Makromolekulare Chemie, Lichtenbergstr. 4, D-85747 Garching, Germany.

Organocatalytic Asymmetric Formal [3+2] Cycloaddition Reaction of Isocyanoesters to Nitroolefins Leading to Highly Optically Active Dihydropyrroles.

Guo C, Xue MX, Zhu MK, Gong LZ.

Hefei National Laboratory for Physical Sciences at the Microscale, Joint Laboratory of Green Synthetic Chemistry and, Department of Chemistry, University of Science and Technology of China, Hefei, 230026, China, Fax: (+86) 551-360-6266.

A Porous Coordination-Polymer Crystal Containing One-Dimensional Water Chains Exhibits Guest-Induced Lattice Distortion and a Dielectric Anomaly.

Cui H, Zhou B, Long LS, Okano Y, Kobayashi H, Kobayashi A.

Institute for Molecular Science, Okazaki 444-8585, Japan.

Do Special Noncovalent pi-pi Stacking Interactions Really Exist?

Grimme S.

Theoretische Organische Chemie, Organisch-Chemisches Institut, Universität Münster, Corrensstrasse 40, 48149 Münster, Germany, Fax: (+49) 251-83-36515.