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Intracellular Adhesion (intracellular + adhesion)
Terms modified by Intracellular Adhesion Selected AbstractsActivation of macrophages and interference with CD4+ T-cell stimulation by Mycobacterium avium subspecies paratuberculosis and Mycobacterium avium subspecies aviumIMMUNOLOGY, Issue 1 2003Susanne Zur Lage Summary Mycobacterium avium subspecies paratuberculosis (M. ptb) and M. avium subspecies avium (M. avium) are closely related but exhibit significant differences in their interaction with the host immune system. The macrophage line, J774, was infected with M. ptb and M. avium and analysed for cytokine production and stimulatory capacity towards antigen-specific CD4+ T cells. Under all conditions J774 cells were activated to produce proinflammatory cytokines. No influence on the expression of major histocompatibility complex (MHC) class II, intracellular adhesion molecule-1 (ICAM-1), B7.1, B7.2 or CD40 was found. However, the antigen-specific stimulatory capacity of J774 cells for a CD4+ T-cell line was significantly inhibited after infection with M. ptb, but not with M. avium. When a T-cell hybridoma expressing a T-cell receptor identical to that of the T-cell line was used, this inhibition was not observed, suggesting that costimulation which is essential for the CD4+ T-cell line is influenced by the pathogenic bacterium M. ptb. [source] The haemopoietic growth factor, Flt3L, alters the immune response induced by transcutaneous immunizationIMMUNOLOGY, Issue 1 2002Maria E. Baca-Estrada Summary Topical application of antigen induces antigen-specific humoral and cellular immune responses. In this study we examined whether expansion of dendritic cells (DC) by Flt3 ligand (Flt3L) treatment influences the induction of immune responses following transcutaneous immunization. Mice were treated intraperitoneally with Flt3L or phosphate-buffered saline (PBS) and immunized transcutaneously with hen egg lysozyme (HEL). Flt3L-treated mice developed lower HEL-specific cellular and humoral immune responses than PBS-treated mice. However, in the presence of cholera toxin (CT), a potent adjuvant for mucosal and transcutaneous immunization, Flt3L-treated mice developed significantly higher cellular and humoral immune responses to HEL when compared to PBS-treated mice. We assessed whether the immunomodulatory effects of CT were a result of activation of epidermal dendritic cells (Langerhans' cells; LC). Our results indicate that within 8,12 hr of topical application of CT, epidermal LC cells lose their dendritic morphology and become rounder in appearance. In addition, we observed enhanced expression of major histocompatibility complex (MHC) class II, and of adhesion molecules CD11c and intracellular adhesion molecule-1 (ICAM-1). Our observations support the concept that the state of activation of DC in the skin is central to the regulation of immune responses. This information is relevant to the design of effective transcutaneous vaccination strategies. [source] Variation in enterovirus receptor genesJOURNAL OF MEDICAL VIROLOGY, Issue 1 2003Ĺse Karttunen Abstract The increased incidence of a enterovirus infections observed in patients with type 1 diabetes preceding the development of the clinical disease could be partially explained by variation in the genes coding for enterovirus receptors. We carried out sequence analysis of the most common enterovirus receptor molecules in 21 diabetic children and 20 healthy adults. DNA was isolated from the leukocytes, and gene regions known to code for virus-recognizing domains in major enterovirus receptors were amplified and sequenced. Heterozygous single-nucleotide polymorphism (SNP), Ala 67 (GCG),,,Thr (ACG), was detected in the poliovirus receptor gene in four individuals in the diabetes group, but not in the control group. However, serological studies could not confirm that this substitution would convey different susceptibility to poliovirus infection. A heterozygous SNP, Lys 29 (AAG),,,Met (ATG), was found in the intracellular adhesion molecule-1 (ICAM-1) (receptor for rhinoviruses and some coxsackie A viruses) in one individual in both groups. A silent SNP in the ,2 integrin subunit gene (echovirus 1 receptor) was frequently found in both groups, a silent heterozygotic SNP in coxsackievirus-adenovirus receptor (coxsackie B virus receptor) gene was seen in one individual in the diabetes group, whereas no variation was found in the DAF (echovirus receptor) and ,3 integrin subunit sequences (receptor for coxsackievirus A9) studied. In conclusion, both synonymous and nonsynonymous sequence variability of genes coding for enterovirus and rhinovirus receptors was shown to occur, but no pattern directly specific for type 1 diabetes was found. J. Med. Virol. 70:99,108, 2003. © 2003 Wiley-Liss, Inc. [source] Sinus CT scans and mediator release in nasal secretions after nasal challenge with cypress pollensALLERGY, Issue 8 2004V. Piette Background:, Involvement of paranasal sinuses has been suggested in allergic rhinitis but not clearly demonstrated. Aims:, To investigate the relationship between intermittent allergic rhinitis and computerized tomography (CT). Methods:, Twenty patients with intermittent rhinitis and sensitized to cypress pollens underwent unilateral nasal provocation tests (NPTs) using increasing concentrations of cypress pollens out of the pollen season. Sinus CT-scans were carried out just before a NPT and 24 h later. Nasal lavage was carried out just before a NPT, 30 min after a positive challenge and again 24 h later. Leucotriene C4/D4, intracellular adhesion molecule-1 and eosinophil cationic protein were measured in nasal secretions. Results:, Thirteen patients (65%) showed an alteration in their CT-scans after allergen challenge. Ten of them showed sinus changes controlateral to their allergenic provocation. Radiological changes mainly affected the osteomeatal complex and the ethmoid sinuses. Pre-existing abnormalities (13 of 20 cases) mainly concerned the maxillary sinuses. There was no correlation between CT-scan abnormalities and levels of mediators released in nasal secretions. Conclusions:, We have shown that nasal allergen challenge can produce radiological changes in the paranasal sinuses. This mainly concerned the ethmoid sinuses. [source] NMR-derived model of interconverting conformations of an ICAM-1 inhibitory cyclic nonapeptideCHEMICAL BIOLOGY & DRUG DESIGN, Issue 3 2003L.O. Sillerud Abstract:, We have produced by phage-display a disulfide-linked cyclic nonapeptide (inhibitory peptide-01, IP01), CLLRMRSIC, that binds to intracellular adhesion molecule-1 (ICAM-1) and blocks binding to its counter-structure, leukocyte functional antigen-1 (LFA-1). As a first step towards improving its pharmacologic properties, we have performed a structural and functional analysis of this peptide inhibitor to determine the features relevant to ICAM-1 binding. We report here the solution model of our initial product, IP01, as derived from two-dimensional nuclear magnetic resonance (NMR) restraints and molecular modeling. Distance and dihedral angle restraints, generated from nuclear Overhauser effect spectroscopy (NOESY) and one-dimensional-NMR experiments respectively, were used to generate an ensemble of structures using distance geometry and simulated annealing. Molecular dynamic simulations produced three interconverting conformational families consistent with the NMR-derived constraints. We describe these conformations and their mechanism of interconversion. Furthermore, we have measured the IC50 s of a series of inhibitors generated from IP01 through alanine substitution of each residue. These results show that the L2-L3-R4-M5-R6 segment is functionally active, conformationally flexible, and contains a ,-turn involving residues R4-S7, while the C1-C9-I8-S7 segment is less functionally-active but adopts a more defined solution conformation, consistent with a scaffolding function. This model will be useful for designing nonpeptide-based organic inhibitors with improved pharmacologic properties. [source] Gold Manno -Glyconanoparticles: Multivalent Systems to Block HIV-1 gp120 Binding to the Lectin DC-SIGN,CHEMISTRY - A EUROPEAN JOURNAL, Issue 38 2009Olga Martínez-Ávila Dr. Abstract The HIV envelope glycoprotein gp120 takes advantage of the high-mannose clusters on its surface to target the C-type lectin dendritic cell-specific intracellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) on dendritic cells. Mimicking the cluster presentation of oligomannosides on the virus surface is a strategy for designing carbohydrate-based antiviral agents. Bio-inspired by the cluster presentation of gp120, we have designed and prepared a small library of multivalent water-soluble gold glyconanoparticles (manno- GNPs) presenting truncated (oligo)mannosides of the high-mannose undecasaccharide Man9GlcNAc2 and have tested them as inhibitors of DC-SIGN binding to gp120. These glyconanoparticles are ligands for DC-SIGN, which also interacts in the early steps of infection with a large number of pathogens through specific recognition of associated glycans. (Oligo)mannosides endowed with different spacers ending in thiol groups, which enable attachment of the glycoconjugates to the gold surface, have been prepared. manno- GNPs with different spacers and variable density of mannose (oligo)saccharides have been obtained and characterized. Surface plasmon resonance (SPR) experiments with selected manno -GNPs have been performed to study their inhibition potency towards DC-SIGN binding to gp120. The tested manno -GNPs completely inhibit the binding from the micro- to the nanomolar range, while the corresponding monovalent mannosides require millimolar concentrations. manno- GNPs containing the disaccharide Man,1-2Man, are the best inhibitors, showing more than 20,000-fold increased activity (100,% inhibition at 115,nM) compared to the corresponding monomeric disaccharide (100,% inhibition at 2.2,mM). Furthermore, increasing the density of dimannoside on the gold platform from 50 to 100,% does not improve the level of inhibition. [source] | |||||||||||||