INTRODUCTION: A critical step preceding the potential biomedical application of nanoparticles is the evaluation of their immunomodulatory effects. Such nanoparticles are expected to enter the bloodstream where they can be recognized and processed by circulating monocytes. Despite the required biocompatibility, this interaction can affect intracellular homeostasis and modulate physiological functions, particularly inflammation. This study focuses on titanium dioxide (TiO2) as an example of relatively low cytotoxic nanoparticles with potential biomedical use and aims to evaluate their possible modulatory effects on the inflammasome-based response in human primary monocytes. METHODS: Monocyte viability, phenotypic changes, and cytokine production were determined after exposure to TiO2 (diameter, 25 nm; P25) alone. In the case of the modulatory effects, we focused on NLRP3 activation. The production of IL-1β and IL-10 was evaluated after (a) simultaneous activation of monocytes with bacterial stimuli muramyl dipeptide (MDP), or lipopolysaccharide (LPS), and TiO2 (co-exposure model), (b) prior activation with TiO2 alone and subsequent exposure to bacterial stimuli MDP or LPS. The differentiation of TiO2-treated monocytes into macrophages and their polarization were also assessed. RESULTS: The selected TiO2 concentration range (30-120 µg/mL) did not induce any significant cytotoxic effects. The highest dose of TiO2 promoted monocyte survival and differentiation into macrophages, with the M2 subset being the most prevalent. Nanoparticles alone did not induce substantial production of inflammatory cytokines IL-1β, IL-6, or TNF-α. The immunomodulatory effect on NLRP3 depended on the type of costimulant used. While co-exposure of monocytes to MDP and TiO2 boosted NLRP3 activity, co-exposure to LPS and TiO2 inhibited NLRP3 by enhancing IL-10 release. The inhibitory effect of TiO2 on NLRP3 based on the promotion of IL-10 was confirmed in a post-exposure model for both costimulants. CONCLUSION: This study confirmed a non-negligible modulatory effect on primary monocytes in their inflammasome-based response and differentiation ability.

• Klíčová slova
• NLRP3, TiO2 nanoparticles, immunomodulation, macrophages, monocytes, polarization,
• MeSH
• acetylmuramyl-alanyl-isoglutamin farmakologie   MeSH
• buněčná diferenciace účinky léků   MeSH
• cytokiny metabolismus   MeSH
• inflamasomy účinky léků   MeSH
• interleukin-10 metabolismus   MeSH
• interleukin-1beta metabolismus   MeSH
• kovové nanočástice chemie   toxicita   MeSH
• kultivované buňky MeSH
• lidé MeSH
• lipopolysacharidy * farmakologie   MeSH
• makrofágy účinky léků   MeSH
• monocyty * účinky léků   MeSH
• nanočástice chemie   toxicita   MeSH
• protein NLRP3 * metabolismus   MeSH
• titan * chemie   farmakologie   toxicita   MeSH
• viabilita buněk * účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetylmuramyl-alanyl-isoglutamin MeSH
• cytokiny MeSH
• inflamasomy MeSH
• interleukin-10 MeSH
• interleukin-1beta MeSH
• lipopolysacharidy * MeSH
• NLRP3 protein, human MeSH Prohlížeč
• protein NLRP3 * MeSH
• titan * MeSH
• titanium dioxide MeSH Prohlížeč

The intestinal microbiota is known to influence postnatal growth. We previously found that a strain of Lactiplantibacillus plantarum (strain LpWJL) buffers the adverse effects of chronic undernutrition on the growth of juvenile germ-free mice. Here, we report that LpWJL sustains the postnatal growth of malnourished conventional animals and supports both insulin-like growth factor-1 (IGF-1) and insulin production and activity. We have identified cell walls isolated from LpWJL, as well as muramyl dipeptide and mifamurtide, as sufficient cues to stimulate animal growth despite undernutrition. Further, we found that NOD2 is necessary in intestinal epithelial cells for LpWJL-mediated IGF-1 production and for postnatal growth promotion in malnourished conventional animals. These findings indicate that, coupled with renutrition, bacteria cell walls or purified NOD2 ligands have the potential to alleviate stunting.

• MeSH
• acetylmuramyl-alanyl-isoglutamin farmakologie   terapeutické užití   MeSH
• buněčná stěna chemie   MeSH
• epitelové buňky mikrobiologie   fyziologie   MeSH
• gnotobiologické modely MeSH
• insulinu podobný růstový faktor I metabolismus   MeSH
• inzulin metabolismus   MeSH
• Lactobacillaceae * fyziologie   MeSH
• myši MeSH
• podvýživa * patofyziologie   terapie   MeSH
• poruchy růstu patofyziologie   terapie   MeSH
• růst * účinky léků   fyziologie   MeSH
• signální adaptorový protein Nod2 * metabolismus   MeSH
• střeva * mikrobiologie   fyziologie   MeSH
• střevní mikroflóra * fyziologie   MeSH
• střevní sliznice mikrobiologie   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetylmuramyl-alanyl-isoglutamin MeSH
• insulinu podobný růstový faktor I MeSH
• inzulin MeSH
• mifamurtide MeSH Prohlížeč
• Nod2 protein, mouse MeSH Prohlížeč
• signální adaptorový protein Nod2 * MeSH

Fatty acyl analogues of muramyldipeptide (MDP) (abbreviated N-L18 norAbuGMDP, N-B30 norAbuGMDP, norAbuMDP-Lys(L18), norAbuMDP-Lys(B30), norAbuGMDP-Lys(L18), norAbuGMDP-Lys(B30), B30 norAbuMDP, L18 norAbuMDP) are designed and synthesized comprising the normuramyl-l-α-aminobutanoyl (norAbu) structural moiety. All new analogues show depressed pyrogenicity in both free (micellar) state and in liposomal formulations when tested in rabbits in vivo (sc and iv application). New analogues are also shown to be selective activators of NOD2 and NLRP3 (inflammasome) in vitro but not NOD1. Potencies of NOD2 and NLRP3 stimulation are found comparable with free MDP and other positive controls. Analogues are also demonstrated to be effective in stimulating cellular proliferation when the sera from mice are injected sc with individual liposome-loaded analogues, causing proliferation of bone marrow-derived GM-progenitors cells. Importantly, vaccination nanoparticles prepared from metallochelation liposomes, His-tagged antigen rOspA from Borrelia burgdorferi, and lipophilic analogue norAbuMDP-Lys(B30) as adjuvant, are shown to provoke OspA-specific antibody responses with a strong Th1-bias (dominance of IgG2a response). In contrast, the adjuvant effects of Alum or parent MDP show a strong Th2-bias (dominance of IgG1 response).

• MeSH
• acetylmuramyl-alanyl-isoglutamin analogy a deriváty   chemie   imunologie   farmakologie   MeSH
• adjuvancia imunologická chemie   farmakologie   MeSH
• antigeny povrchové chemie   imunologie   farmakologie   MeSH
• bakteriální vakcíny chemie   imunologie   farmakologie   MeSH
• Borrelia burgdorferi imunologie   MeSH
• HEK293 buňky MeSH
• imunizace MeSH
• lidé MeSH
• lipoproteiny chemie   imunologie   farmakologie   MeSH
• lymeská nemoc imunologie   mikrobiologie   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• protein NLRP3 agonisté   imunologie   MeSH
• proteiny vnější bakteriální membrány chemie   imunologie   farmakologie   MeSH
• RAW 264.7 buňky MeSH
• tvorba protilátek MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetylmuramyl-alanyl-isoglutamin MeSH
• adjuvancia imunologická MeSH
• antigeny povrchové MeSH
• bakteriální vakcíny MeSH
• glucosaminylmuramyl-2-alanine-D-isoglutamine MeSH Prohlížeč
• lipoproteiny MeSH
• OspA protein MeSH Prohlížeč
• protein NLRP3 MeSH
• proteiny vnější bakteriální membrány MeSH

INTRODUCTION: Crohn's disease (CD) is a disabling chronic enteropathy sustained by a harmful T-cell response toward antigens of the gut microbiota in genetically susceptible subjects. Growing evidence highlights the safety and possible efficacy of mesenchymal stem cells (MSCs) as a new therapeutic tool for this condition. Therefore, we aimed to investigate the effects of bone marrow-derived MSCs on pathogenic T cells with a view to clinical application. METHODS: T-cell lines from both inflamed and non-inflamed colonic mucosal specimens of CD patients and from healthy mucosa of control subjects were grown with the antigen muramyl-dipeptide in the absence or presence of donors' MSCs. The MSC effects were evaluated in terms of T-cell viability, apoptotic rate, proliferative response, immunophenotype, and cytokine profile. The role of the indoleamine 2,3-dioxygenase (IDO) was established by adding a specific inhibitor, the 1-methyl-DL-tryptophan, and by using MSCs transfected with the small interfering RNA (siRNA) targeting IDO. The relevance of cell-cell contact was evaluated by applying transwell membranes. RESULTS: A significant reduction in both cell viability and proliferative response to muramyl-dipeptide, with simultaneous increase in the apoptotic rate, was found in T cells from both inflamed and non-inflamed CD mucosa when co-cultured with MSCs and was reverted by inhibiting IDO activity and expression. A reduction of the activated CD4(+)CD25(+) subset and increase of the CD3(+)CD69(+) population were also observed when T-cell lines from CD mucosa were co-cultured with MSCs. In parallel, an inhibitory effect was evident on the expression of the pro-inflammatory cytokines tumor necrosis factor-α, interferon-γ, interleukin-17A and -21, whereas that of the transforming growth factor-β and interleukin-6 were increased, and production of the tolerogenic molecule soluble HLA-G was high. These latter effects were almost completely eliminated by blocking the IDO, whose activity was upregulated in MSCs co-cultured with CD T cells. The use of a semipermeable membrane partially inhibited the MSC immunosuppressive effects. Finally, hardly any effects of MSCs were observed when T cells obtained from control subjects were used. CONCLUSION: MSCs exert potent immunomodulant effects on antigen-specific T cells in CD through a complex paracrine and cell-cell contact-mediated action, which may be exploited for widespread therapeutic use.

• MeSH
• acetylmuramyl-alanyl-isoglutamin farmakologie   MeSH
• antigeny povrchové metabolismus   MeSH
• apoptóza účinky léků   MeSH
• buňky kostní dřeně cytologie   MeSH
• časosběrné zobrazování MeSH
• Crohnova nemoc patologie   MeSH
• cytokiny metabolismus   MeSH
• dospělí MeSH
• HLA-G antigeny metabolismus   MeSH
• imunofenotypizace MeSH
• indolamin-2,3,-dioxygenasa antagonisté a inhibitory   genetika   metabolismus   MeSH
• kokultivační techniky MeSH
• kultivované buňky MeSH
• lidé středního věku MeSH
• lidé MeSH
• malá interferující RNA metabolismus   MeSH
• mezenchymální kmenové buňky cytologie   metabolismus   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• proliferace buněk účinky léků   MeSH
• RNA interference MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• střevní sliznice cytologie   MeSH
• T-lymfocyty cytologie   účinky léků   imunologie   MeSH
• tryptofan analogy a deriváty   farmakologie   MeSH
• viabilita buněk MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1-methyltryptophan MeSH Prohlížeč
• acetylmuramyl-alanyl-isoglutamin MeSH
• antigeny povrchové MeSH
• cytokiny MeSH
• HLA-G antigeny MeSH
• indolamin-2,3,-dioxygenasa MeSH
• malá interferující RNA MeSH
• tryptofan MeSH

PURPOSE: The aim of this work was to demonstrate an immunostimulatory and adjuvant effect of new apyrogenic lipophilic derivatives of norAbuMDP and norAbuGMDP formulated in nanoliposomes. METHODS: Nanoliposomes and metallochelating nanoliposomes were prepared by lipid film hydration and extrusion methods. The structure of the liposomal formulation was studied by electron microscopy, AF microscopy, and dynamic light scattering. Sublethal and lethal γ-irradiation mice models were used to demonstrate stimulation of innate immune system. Recombinant Hsp90 antigen (Candida albicans) bound onto metallochelating nanoliposomes was used for immunisation of mice to demonstrate adjuvant activities of tested compounds. RESULTS: Safety and stimulation of innate and adaptive immunity were demonstrated on rabbits and mice. The liposomal formulation of norAbuMDP/GMDP was apyrogenic in rabbit test and lacking any side effect in vivo. Recovery of bone marrow after sublethal γ-irradiation as well as increased survival of mice after lethal irradiation was demonstrated. Enhancement of specific immune response was demonstrated for some derivatives incorporated in metallochelating nanoliposomes with recombinant Hsp90 protein antigen. CONCLUSIONS: Liposomal formulations of new lipophilic derivatives of norAbuMDP/GMDP proved themselves as promising adjuvants for recombinant vaccines as well as immunomodulators for stimulation of innate immunity and bone-marrow recovery after chemo/radio therapy of cancer.

• MeSH
• acetylmuramyl-alanyl-isoglutamin aplikace a dávkování   analogy a deriváty   chemie   farmakologie   terapeutické užití   MeSH
• adaptivní imunita účinky léků   MeSH
• adjuvancia imunologická aplikace a dávkování   chemie   farmakologie   terapeutické užití   MeSH
• analýza přežití MeSH
• antigeny fungální imunologie   MeSH
• experimentální radiační poranění imunologie   prevence a kontrola   MeSH
• králíci MeSH
• liposomy MeSH
• mikroskopie atomárních sil MeSH
• mikroskopie elektronová rastrovací MeSH
• molekulární struktura MeSH
• myši inbrední ICR MeSH
• myši MeSH
• nanočástice MeSH
• nosiče léků chemie   MeSH
• přirozená imunita účinky léků   MeSH
• proteiny tepelného šoku HSP90 imunologie   MeSH
• protilátky fungální krev   MeSH
• rekombinantní proteiny imunologie   MeSH
• transmisní elektronová mikroskopie MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetylmuramyl-alanyl-isoglutamin MeSH
• adjuvancia imunologická MeSH
• antigeny fungální MeSH
• glucosaminylmuramyl-2-alanine-D-isoglutamine MeSH Prohlížeč
• liposomy MeSH
• N-acetylmuramyl-aminobutyryl-isoglutamine MeSH Prohlížeč
• nosiče léků MeSH
• proteiny tepelného šoku HSP90 MeSH
• protilátky fungální MeSH
• rekombinantní proteiny MeSH

BACKGROUND: Genetic and functional studies have associated variants in the NOD2/CARD15 gene with Crohn's disease. AIMS: This study aims to replicate the association of three common NOD2 mutations with Crohn's disease, study its effect on NOD2 expression in B cells and its interaction with other IBD-associated genes. METHODS: A total of 294 IBD patients (179 familial IBD, 115 sporadic IBD) and 298 unrelated healthy controls were from central Pennsylvania. NOD2 mutations were analyzed by primer-specific amplification, PCR based-RFLP, and validated with the ABI SNPlexM genotyping system. Gene-gene interaction was studied using a statistical model for epistasis analysis. RESULTS: Three common NOD2 mutations are associated with Crohn's disease (p=5.08×10(-7), 1.67×10(-6), and 1.87×10(-2) for 1007fs, R720W, and G908R, respectively), but not with ulcerative colitis (p=0.1046, 0.1269, and 0.8929, respectively). For IBD overall, 1007finsC (p=4.4×10(-5)) and R720W (p=9.24×10(-5)) were associated with IBD, but not G908R (p=0.1198). We revealed significant interactions of NOD2 with other IBD susceptibility genes IL23R, DLG5, and OCTN1. We discovered that NOD2 was expressed in both normal human peripheral blood B cells and in EBV-transformed B cell lines. Moreover, we further demonstrated that muramyl dipeptide (MDP) stimulation of B lymphocytes up-regulated expression of NF-κB-p50 mRNA. CONCLUSION: NOD2 is expressed in peripheral B cells, and the up-regulation of NOD2 expression by MDP was significantly impaired by NOD2 mutations. The finding suggests a possible role of NOD2 in the immunological response in IBD pathogenesis.

• MeSH
• acetylmuramyl-alanyl-isoglutamin imunologie   MeSH
• B-lymfocyty metabolismus   MeSH
• genetická epistáze MeSH
• idiopatické střevní záněty genetika   imunologie   MeSH
• lidé MeSH
• membránové proteiny genetika   MeSH
• mutace MeSH
• nádorové supresorové proteiny genetika   MeSH
• NF-kappa B - podjednotka p50 metabolismus   MeSH
• proteiny přenášející organické kationty genetika   MeSH
• receptory interleukinů genetika   MeSH
• signální adaptorový protein Nod2 genetika   fyziologie   MeSH
• studie případů a kontrol MeSH
• symportéry MeSH
• upregulace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetylmuramyl-alanyl-isoglutamin MeSH
• DLG5 protein, human MeSH Prohlížeč
• IL23R protein, human MeSH Prohlížeč
• membránové proteiny MeSH
• nádorové supresorové proteiny MeSH
• NF-kappa B - podjednotka p50 MeSH
• NFKB1 protein, human MeSH Prohlížeč
• NOD2 protein, human MeSH Prohlížeč
• proteiny přenášející organické kationty MeSH
• receptory interleukinů MeSH
• signální adaptorový protein Nod2 MeSH
• SLC22A4 protein, human MeSH Prohlížeč
• symportéry MeSH

Lyme disease caused by spirochete Borrelia burgdorferi sensu lato, is a tick-born illness. If the infection is not eliminated by the host immune system and/or antibiotics, it may further disseminate and cause severe chronic complications. The immune response to Borrelia is mediated by phagocytic cells and by Borrelia-specific complement-activating antibodies associated with Th1 cell activation. A new experimental vaccine was constructed using non-lipidized form of recombinant B. burgdorferi s.s. OspC protein was anchored by metallochelating bond onto the surface of nanoliposomes containing novel nonpyrogenic lipophilized norAbuMDP analogues denoted MT05 and MT06. After i.d. immunization, the experimental vaccines surpassed Alum with respect to OspC-specific titers of IgG2a, IgG2b isotypes when MT06 was used and IgG3, IgM isotypes when MT05 was used. Both adjuvants exerted a high adjuvant effect comparable or better than MDP and proved themselves as nonpyrogenic.

• MeSH
• acetylmuramyl-alanyl-isoglutamin chemie   toxicita   MeSH
• antigeny bakteriální imunologie   MeSH
• Borrelia burgdorferi imunologie   MeSH
• chelátory chemie   toxicita   MeSH
• diferenciální skenovací kalorimetrie MeSH
• elektroforéza v polyakrylamidovém gelu MeSH
• ELISA MeSH
• liposomy MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• nanočástice chemie   toxicita   MeSH
• nosiče léků chemie   toxicita   MeSH
• proteiny vnější bakteriální membrány imunologie   MeSH
• protilátky bakteriální krev   MeSH
• radiační rozptyl MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
• světlo MeSH
• transmisní elektronová mikroskopie MeSH
• vakcína proti lymeské nemoci aplikace a dávkování   imunologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetylmuramyl-alanyl-isoglutamin MeSH
• antigeny bakteriální MeSH
• chelátory MeSH
• liposomy MeSH
• nosiče léků MeSH
• OspC protein MeSH Prohlížeč
• proteiny vnější bakteriální membrány MeSH
• protilátky bakteriální MeSH
• vakcína proti lymeské nemoci MeSH

Lysozyme is a widely distributed antimicrobial protein having specificity for cleaving the beta-(1,4)-glycosidic bond between N-acetylmuramic acid (NAM) and N-acetylglucosamine (GlcNAc) of peptidoglycan of the bacterial cell walls and thus efficiently contributes to protection against infections caused mainly by Gram-positive bacteria. In the present study, we assembled a full-length cDNA of a novel invertebrate-type lysozyme from Eisenia andrei earthworm (EALys) by RT-PCR and RACE system. The primary structure of EALys shares high homology with other invertebrate lysozymes; however the highest, 72% identity, was shown for the destabilase I isolated from medicinal leech. Recombinant EALys expressed in Escherichia coli exhibited the lysozyme and isopeptidase activity. Moreover, real-time PCR revealed increased levels of lysozyme mRNA in coelomocytes of E. andrei after the challenge with both Gram-positive and Gram-negative bacteria.

• MeSH
• Bacillus subtilis imunologie   patogenita   MeSH
• bakteriální adheze MeSH
• chitinasy metabolismus   MeSH
• Echinodermata genetika   MeSH
• endopeptidasy metabolismus   MeSH
• Escherichia coli genetika   imunologie   patogenita   MeSH
• glukosamin analogy a deriváty   imunologie   metabolismus   MeSH
• grampozitivní bakteriální infekce imunologie   MeSH
• hydrolýza MeSH
• infekce vyvolané Escherichia coli imunologie   MeSH
• interakce hostitele a patogenu MeSH
• klonování DNA MeSH
• kyseliny muramové imunologie   metabolismus   MeSH
• lyasy štěpící vazby C-N metabolismus   MeSH
• muramidasa genetika   imunologie   metabolismus   MeSH
• Oligochaeta enzymologie   genetika   imunologie   MeSH
• pijavka lékařská genetika   MeSH
• sekvenční homologie MeSH
• virulence MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chitinasy MeSH
• endopeptidasy MeSH
• fibrin destabilase MeSH Prohlížeč
• glukosamin MeSH
• isopeptidase MeSH Prohlížeč
• kyseliny muramové MeSH
• lyasy štěpící vazby C-N MeSH
• muramidasa MeSH
• N-acetylglucopyranosylamine MeSH Prohlížeč
• N-acetylmuramic acid MeSH Prohlížeč

The aim of this study was to investigate development over time of the surface expression of CD44 on macrophages during an inflammatory response of bovine mammary gland. Intramammary instillation of muramyl dipeptide (MDP) and lipopolysaccharide (LPS) resulted in a significant increase in the total count of CD44+ non-vacuolised macrophages ((N)MAC) after 24h. During resolution of the inflammatory response, there was observed a gradual decrease in the total count CD44+ (N)MAC. The lower total count and proportion of CD44+vacuolised macrophages ((V)MAC) was observed as the effect of MDP and LPS at 24h after induction (P<0.01). During resolution, the total count and proportion of CD44+(V)MAC increased. We have demonstrated CD44 receptor is expressed during the inflammatory response caused by LPS and MDP and the effect of these components on CD44 expression was particularly evident during initiation of the inflammatory response. High expression of CD44 in resolution of inflammatory response may relate to macrophages involvement in the processes leading to restitution of injured tissues.

• MeSH
• acetylmuramyl-alanyl-isoglutamin imunologie   MeSH
• antigeny CD44 biosyntéza   imunologie   MeSH
• lipopolysacharidy imunologie   MeSH
• makrofágy imunologie   ultrastruktura   MeSH
• mastitida skotu imunologie   MeSH
• nemoci skotu imunologie   MeSH
• neparametrická statistika MeSH
• počet buněk veterinární   MeSH
• průtoková cytometrie veterinární   MeSH
• skot MeSH
• transmisní elektronová mikroskopie veterinární   MeSH
• zvířata MeSH
• Check Tag
• skot MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetylmuramyl-alanyl-isoglutamin MeSH
• antigeny CD44 MeSH
• lipopolysacharidy MeSH

The need for safe and structurally defined immunomodulators and adjuvants is increasing in connection with the recently observed marked increase in the prevalence of pathological conditions characterized by immunodeficiency. Important groups of such compounds are muramyl glycopeptides, analogs of muramyl dipeptide (MDP), glucosaminyl-muramyl dipeptide (GMDP), and desmuramylpeptides. We have designed and synthesized new types of analogs with changes in both the sugar and the peptide parts of the molecule that show a high immunostimulating and adjuvant activity and suppressed adverse side effects. The introduction of lipophilic residues has also improved their incorporation into liposomes, which represent a suitable drug carrier. The proliposome-liposome method is based on the conversion of the initial proliposome preparation into liposome dispersion by dilution with the aqueous phase. The description of a home-made stirred thermostated cell and its link-up with a liquid delivery system for a rapid and automated preparation of multilamellar liposomes at strictly controlled conditions (sterility, temperature, dilution rate and schedule) is presented. The cell has been designed for laboratory-scale preparation of liposomes (300-1000 mg of phospholipid per run) in a procedure taking less than 90 min. The method can be readily scaled up. Examples of adjuvant and immunostimulatory effect of liposomal preparation in mice model will be presented.

• MeSH
• acetylmuramyl-alanyl-isoglutamin škodlivé účinky   analogy a deriváty   chemie   farmakologie   MeSH
• adjuvancia imunologická škodlivé účinky   chemická syntéza   chemie   farmakologie   MeSH
• liposomy * škodlivé účinky   chemická syntéza   chemie   MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetylmuramyl-alanyl-isoglutamin MeSH
• adjuvancia imunologická MeSH
• glucosaminylmuramyl-2-alanine-D-isoglutamine MeSH Prohlížeč
• liposomy * MeSH