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Immunoglobulin A (IgA) is notable for its broad specificity toward multiple bacteria. Phosphorylcholine (PC) plays a role in the infection of pathogenic bacteria carrying PC and in the induction of IgA responses in the host immune system. The commercially available mouse monoclonal IgA, TEPC15-IgA, is a distinctive antibody with specificity for PC, warranting further exploration of its response to PC-bearing enteric bacteria. In this study, using 17 different enteric bacteria, including 3 aerobic and 14 anerobic bacteria that could be cultured in vitro, we confirmed that TEPC15-IgA recognizes 4 bacterial species: Lactobacillus taiwanensis, Limosilactobacillus frumenti, Streptococcus infantis, and Escherichia coli, although reactivity varied. Interestingly, TEPC15-IgA did not react with four of six Lactobacillus species used. Moreover, distinct target molecules associated with PC in L. taiwanensis and L. frumenti were evident, differing in molecular weight. These findings suggest that the natural generation of PC-specific IgA could prevent PC-mediated infections and potentially facilitate the formation of a microflora rich in indigenous bacteria with PC, particularly in the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Poly(2-methacryloyloxyethyl choline methylphosphonate) (PMCP) containing choline phosphonate groups, which consist of quaternary ammonium and anionic phosphonate groups in reverse order to that of phosphorylcholine, was synthesized via controlled radical polymerization. PMCP formed aggregates in water through electrostatic interactions. Meanwhile, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) having a similar structure to that of PMCP was dissolved as a unimer in both water and salt solutions. [ABSTRACT FROM AUTHOR]

Manipulating the surface and substrate of cross-linked polyethylene (CLPE) is an essential approach for obtaining life-long orthopedic bearings. We therefore proposed a bearing material comprised of an antioxidative substrate generated by vitamin E blending (HD-CLPE[VE]) with a poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)-grafted surface, and investigated its wear resistance and oxidative stability under accelerated aging and load bearing conditions. Neither the hydration nor friction kinetics of the molecular network structure of the PMPC-grafted surface or the HD-CLPE(VE) substrate were influenced by accelerated aging but rather exhibited high stability even under high oxidation conditions. The characteristics of the PMPC-grafted surface improved the wear and impact fatigue resistance of the HD-CLPE(VE) liner regardless of accelerated aging. Notably, the PMPC-grafted surface was found to affect the potential oxidative stability at the rim part of the acetabular liner. PMPC chains serve several important functions on the surface regardless of load bearing, such as high lubricity or low lipophilicity attributed to phosphorylcholine groups and/or surrounding water-fluid film, and suppression of lipid diffusion attributed to methacrylate main chains on the surface. Together, these results provide preliminary evidence that the PMPC graft layer and vitamin E-blended substrate might positively affect the extent of orthopedic implant durability. [ABSTRACT FROM AUTHOR]

Copyright of Kobunshi Ronbunshu is the property of Society of Polymer Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A crosslinkable zwitterionic copolymer PMBT was coated onto the surfaces of polypropylene hollow fiber membrane (PP-HFM) oxygenator and its connecting tubes. The PMBT copolymer coating on the oxygenator circuit formed a cell outer membrane mimetic surface with excellent stability. The hemocompatibility of the PMBT copolymer coated PP-HFM oxygenator circuit was evaluated by animal extracorporeal circulation. The concentrations of clotting components fibrinogen and platelet in the blood were almost unchanged during the circulation through the PMBT copolymer coated oxygenator circuits. By contrast, the concentrations of fibrinogen and platelet were significantly reduced to 52% and 56% respectively in the uncoated oxygenator group due to adsorption and thrombogenesis of the blood during 2 h circulation. Moreover, concentration of activation marker beta-thromboglobulin for platelet in the blood was remarkably lower in the PMBT group than the uncoated control group ( p < 0.01). All the results strongly supported that the hemocompatibility of the PP-HFM oxygenator circuit could be improved significantly by coating a stable and densely assembled zwitterionic polymer film. This simple, stable and highly effective cell membrane mimetic coating strategy may be applicable in developing advanced oxygenator systems and other artificial organs. Statement of Significance Although a number of studies have reported the fabrication of zwitterionic phosphorylcholine coated oxygenators to resist the adsorption and activation of blood components and eliminate heparin-induced thrombocytopenia, none of them have fabricated stable and densely assembled film, especially with crosslinkable amphiphilic random copolymer described in our manuscript. The novel features of our work include: • The first study of fabricating crosslinked and densely assembled zwitterionic copolymer coating on surfaces of a commercial oxygenator system. • The first study on hemocompatibility of both the PMBT coated and the bare commercial PP-HFM oxygenator circuits by animal extracorporeal circulation. • Much better hemocompatibility was measured on the PMBT coated oxygenator circuit compared with the bare and other polymer coated oxygenator systems. [ABSTRACT FROM AUTHOR]

Understanding of the activation dynamics of C-reactive protein (CRP) on plasma membranes is important in the development of zwitterionic biomaterials for their uses in the tissues of inflammation and infection. Previously, the use of a zwitterionic phosphorylcholine group, a biomimetic ligand for CRP in the presence of calcium ions, for binding experiments has revealed that the adsorption dynamics changed by ionic microenvironments. Here we focused on the effect of the ligand density on a surface, a major physicochemical parameter, on the multivalent binding modes. A building block from synthetic origin, a phospholipid analogue with thiol ends, was developed for making a cell membrane-mimicked self-assembled monolayers with tunable lateral ligand density on the molecular basis. The multivalent binding kinetics of CRP, a pentraxin in the original conformation, onto the engineered surface was measured using a surface plasmon resonance technique. The binding experiments revealed that the on-rate and off-rate constants in the first ligand-occupation reaction increased with increasing the ligand density, which resulted in stable values of the dissociation constant. Notably, the binding affinity in the second ligand-occupation reaction showed the optimal value as a function of the ligand density. Moreover, the binding experiments using a monomeric CRP-specific DNA aptamer revealed that pentameric CRP underwent structural transition into the monomers following the adsorption onto the surfaces via multivalent contacts in a pH-dependent manner. The bioengineering-based approach reveals for the first time how the multiple binding reaction is altered by the ligand arrangement at the molecular resolution and how CRP is activated by the conformational transition induced by the multiplex bindings. Statement of Significance C-reactive protein (CRP), a major acute-phase pentraxin, binds to plasma membranes through the multivalent contacts with zwitterionic phosphorylcholine groups. However, details in the molecular dynamics is unknown due to a lack of proper sensing platform. The paper describe the synthesis of thiol-functionalized phosphorylcholine for the development of a robust cell membrane-mimetic surface on a surface plasmon resonance sensor at desired lateral ligand densities. The engineered approach on molecular basis enables a rigorous arrangement of the ligand on the surface, whose tunability and robustness are not achieved using conventional supported lipid layers. The effect of the ligand density on the multivalent binding kinetics provides the understanding of how the multivalent contacts induce conformational transitions of CRP and responses to inflammation. [ABSTRACT FROM AUTHOR]

Copyright of Kobunshi Ronbunshu is the property of Society of Polymer Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Polymeric micelles with cell outer membrane mimetic structure were prepared in water from amphiphilic random copolymers bearing both the hydrophilic phosphorylcholine zwitterions and hydrophobic octadecyl side chains of cell outer membrane. The polymeric micelles showed sizes ranging from 80 nm to 120 nm in hydrodynamic diameter and zeta-potentials from −6.4 mV to −2.4 mV by dynamic light scattering measurements. The micelles loaded with 6-coumarin as a fluorescence probe were stable to investigate their blood circulation and biodistribution. The in vitro phagocytosis results using murine peritoneal macrophages showed 10-fold reduction compared with a reference micelle. The in vivo blood circulation half-life of the polymeric micelles following intravenous administration in New Zealand Rabbits was increased from 0.55 h to 90.5 h. More interestingly, tissue distribution results showed that the concentration of the micelles in the kidney is 4-fold higher than that in the liver and other organs 48 h after administration. The results of this work show great promise for designing more effective stealth drug carriers that can minimize reticuloendothelial system clearance and circulate for long time to reach target by using simple cell membrane mimetic random copolymer micelles. [ABSTRACT FROM AUTHOR]

Despite their popular use in breast augmentation and reconstruction surgeries, the limited biocompatibility of silicone implants can induce severe side effects, including capsular contracture – an excessive foreign body reaction that forms a tight and hard fibrous capsule around the implant. This study examines the effects of using biomembrane-mimicking surface coatings to prevent capsular formations on silicone implants. The covalently attached biomembrane-mimicking polymer, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), prevented nonspecific protein adsorption and fibroblast adhesion on the silicone surface. More importantly, in vivo capsule formations around PMPC-grafted silicone implants in rats were significantly thinner and exhibited lower collagen densities and more regular collagen alignments than bare silicone implants. The observed decrease in α-smooth muscle actin also supported the alleviation of capsular formations by the biomembrane-mimicking coating. Decreases in inflammation-related cells, myeloperoxidase and transforming growth factor-β resulted in reduced inflammation in the capsular tissue. The biomembrane-mimicking coatings used on these silicone implants demonstrate great potential for preventing capsular contracture and developing biocompatible materials for various biomedical applications. [ABSTRACT FROM AUTHOR]

Abstract: In order to create suitable biocompatible materials for various tissue engineering applications, it is important to be able to understand protein adsorption and cell adhesion behaviors on the material’s surfaces. It is known that the nanoscale distribution of adsorbed proteins affects cell adhesion behaviors. However, how nanoscale structures affect cell adhesion behaviors is still unclear. Therefore, in this study, we investigate the effect of the distribution of adsorbed proteins by the phase reversal of amphiphilic block copolymers composed of protein-non-adsorptive poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and protein-adsorptive poly(3-methacryloyloxy propyltris(trimethylsilyloxy) silane) (PMPTSSi) on cell adhesion behaviors. The nanodomain structures of phase-separated block copolymers were successfully confirmed using transmission electron microscopy and atomic force microscopy. Surfaces that had PMPC dot-like domains (23±4nm) and ones that had PMPTSSi dot-like domains (25±6nm) were made. From protein adsorption and L929 cell adhesion measurements, it was found that even on surfaces with equal quantities of protein adsorption, the number of cells on surfaces with PMPC dot-like domains was larger than those with PMPTSSi dot-like domains. This suggests that the simple phase-reversal of the distribution of adsorbed proteins can be used to affect cell adhesion behaviors for designing biomaterial surfaces for tissue engineering applications. [Copyright &y& Elsevier]

The preparation of soluble polyamides, poly(amide-ester) and poly(urethane-urea) containing phosphorylcholine (PC) group was carried out by the polycondensation and polyaddition using an aromatic diamine monomer containing a phospholipid polar group. In the syntheses of poly(amide-ester) and poly(urethane-urea), polycarbonatediol was used as a comonomer to insert a soft segment. The self-standing elastic polymer films could be fabricated from the obtained PC-containing copolymers by the solvent-casting method. In particular, polymer films fabricated from poly(urethane-urea) exhibited the elastic properties similar to commercially available poly(carbonate-urethane), bionate®. It was found that the PC-containing polymer films sufficiently reduced the adhesion of proteins and platelets. Therefore, it was shown that the obtained polymers possess both, high biocompatibility derived from PC group and the elastic properties derived from the main chain structure. [ABSTRACT FROM AUTHOR]

Abstract: Background: We have reported that anti-phosphorylcholine (anti-PC) IgM is a protection marker for human cardiovascular disease (CVD) and atherosclerosis. We here investigate the anti-PC autoantibodies in a well-defined cohort with regard to idiotype, atherosclerosis progression and mechanisms for its protective action. Methods: Serum levels and binding specificities of different anti-PC isotypes were determined in 226 hypertensive individuals enrolled in European Lacidipine Study on Atherosclerosis using ELISA. The mean of the maximum Intima-Media Thicknesses (IMT) in the far walls of common carotids and bifurcations was assessed at the time of inclusion, and four years afterwards. Apoptosis in immune cells was induced with lysophosphatidylcholine (LPC) and quantified using the MTT-assay. Results: Anti-PC IgM, IgA and IgG1 (but not IgG2) was negatively associated with IMT-progression. Combining anti-PC IgM with data on antibodies against oxidized- and malondialdehyde-modified LDL further strengthened this association. At very high levels, anti-PC IgM exhibited a striking negative association with atherosclerosis progression (OR 0.05; CI 0.006–0.40). Analysis of serum samples taken four years apart in study participants affirmed the stability of anti-PC IgM titers over time. Examination of fine specificities revealed that the protective isotypes (IgM, IgA and IgG1) are of the Group I idiotype whereas the non-protective IgG2 subclass was Group II. Anti-PC IgM inhibited LPC-induced cell death of immune cells. Conclusion: Group I anti-PC antibodies, particularly of the IgM class, are independent protection markers for atherosclerosis progression. One potential mechanism of action is inhibition of LPC-induced cell cytotoxicity. [Copyright &y& Elsevier]

The synthesis of a novel aromatic diamine compound containing phosphorylcholine (PC) group was carried out to prepare aromatic polyamides with PC moiety, in order to develop durable biocompatible polymer materials. The desired diamine compound, 2-(3,5-diaminophenylcarbonyloxy)ethyl phosphorylcholine (DAPC), was prepared from a reaction of 2-[2-(3,5-dinitrophenylcarbonyloxy)ethyl]-2-oxo-1,3,2-dioxaphospholane with trimethylamine, followed by the reduction of the dinitro group by H2/Pd. The starting phospholane compound was synthesized by a condensation reaction of 2-hydroxyethyl 3,5-dinitrobenzoate with 2-chloro-2-oxo-1,3,2-dioxaphospholane. The polycondensation of DAPC with 4,4′-diamino-3,3′-dimethyldiphenylmethane and isophthaloyl chloride gave the copolyamides with different PC contents. From the results of contact angle of water and XPS analysis on the surface of the copolyamide coating films, it was found that PC units were concentrated on the surface after immersed in water. In addition, by using 2,2-bis[4-(aminophenyloxy)phenyl]propane or 2,2-bis[4-(aminophenyloxy)phenyl]hexafluoropropane as a diamine comonomer with DAPC, high molecular weight copolyamides containing PC moiety were obtained to prepare homogeneous coating films. The obtained copolyamides exhibited the high thermal stability, and also the excellent biocompatibility even though the content of PC monomer unit in the copolymer was around 20 mol %, which was confirmed by the platelet adhesion test. Therefore, the introduction of PC group in the side chain of aromatic polyamide was effective to develop the biocompatibility, which would be due to the surface property covered with polar PC units. [ABSTRACT FROM AUTHOR]

Background: Sera from patients with periodontal attachment loss contain higher concentrations of IgG anti-phosphorylcholine (anti-PC) than sera from healthy subjects. Furthermore, a large proportion of plaque bacteria bear PC-containing surface antigens, implicating the oral flora as a source of immunogen for anti-PC. Additionally, anti-PC is cross-reactive with a variety of oral bacterial antigens and human antigens such as oxidized low-density lipoprotein (oxLDL). We hypothesized that, if the oral flora is a source of PC antigens, then we should be able to detect local anti-PC and anti-oxLDL production in gingival crevicular fluid (GCF). Methods: To test this, we collected 66 GCF samples from 15 patients with aggressive periodontitis and examined both the GCF samples and serum samples for their content of IgG anti-PC, IgG anti-LDL, and IgG anti-oxLDL by enzyme-linked immunosorbent assay. We also determined levels of anti-tetanus toxoid (anti-TT) as a non-oral antigen control. Serum and GCF concentrations of serum albumin (HSA) were also determined for use as a dilution marker. A conservative GCF:serum antibody ratio of greater than 1.5 was considered to be evidence of local antibody production. Results: For the non-oral antigen TT, only one out of 62 samples contained locally produced antibody. Eight out of 64 samples (7 from a single subject) demonstrated local production of anti-LDL. In contrast, 28 out of 66 samples demonstrated local production of anti-PC, and 47 out of 66 samples contained locally produced anti-oxLDL. It was observed that A. actinomycetemcomitans strains containing or devoid of PC could absorb anti-oxLDL from human sera. Although there was a correlation between the ratios of anti-PC and anti-oxLDL (Spearman's rho = 0.35, P = 0.0037), local production of both antibodies was found in only 17 out of 65 samples, indicating that these antibodies are not always reflective of reactivity to the same antigens. Conclusion: The local production of anti-PC and anti-oxLDL further implicates the oral flora as a source of antigen that may mediate immune reactions of relevance to cardiovascular and other systemic diseases. [ABSTRACT FROM AUTHOR]