Disease relevance of D-Mannuronate

• The alginate capsule produced by the human pathogen Pseudomonas aeruginosa is composed mainly of mannuronic acid polymers (poly-M) that have immunostimulating properties [1].
• Alginate (Alg), a random polymer of mannuronic acid and glucuronic acid residues, is synthesized and secreted by Pseudomonas aeruginosa primarily during its infection of the lungs of cystic fibrosis patients [2].
• The effects of alginate composition on cell growth as well as the metabolic and secretory profile of transformed beta-cells entrapped in alginate/poly-L-lysine/alginate (APA) solid beads were investigated following entrapment of beta TC3 mouse insulinoma cells in alginate composed of either high mannuronic acid or high guluronic acid residues [3].

High impact information on D-Mannuronate

• We have determined that key factors responsible for these past failures include cytokine (interleukins 1 and 6 and tumor necrosis factor) stimulation by mannuronic acid monomers from alginate capsules with weak mechanical integrity, which results in fibroblast proliferation [4].
• Involvement of toll-like receptor (TLR) 2 and TLR4 in cell activation by mannuronic acid polymers [1].
• Involvement of CD14 and beta2-integrins in activating cells with soluble and particulate lipopolysaccharides and mannuronic acid polymers [5].
• Induction of tumor necrosis factor production from monocytes stimulated with mannuronic acid polymers and involvement of lipopolysaccharide-binding protein, CD14, and bactericidal/permeability-increasing factor [6].
• The biological properties of MEP were also shown to be dependent on the structural integrity of the O-acetyl groups substituted for the mannuronic acid residues [7].

Biological context of D-Mannuronate

• The average degree of acetylation was 16%, and the ratio of mannuronic acid to gluluronic acid was 4 [8].
• Conversely, betaTC3 cells encapsulated in alginates with a high mannuronic acid content experienced a rapid increase in metabolic and secretory activity as a result of rapid cell growth [9].
• 5. Only mannuronic acid was detected at the reducing end of fragments after exhausive enzymolysis, reduction and hydrolysis [10].

Anatomical context of D-Mannuronate

• Stimulation of various functions in murine peritoneal macrophages by high mannuronic acid-containing alginate (HMA) exposure in vivo [11].
• The in vivo immunomodulatory function of the activity of murine natural killer (NK) cells induced by high mannuronic acid-containing alginate (HMA) was examined [12].
• Islets of Langerhans were isolated from WAGola rats and encapsulated in high mannuronic acid sodium alginate droplets [13].
• The degree of response was not affected by capsule composition in the renal subcapsular space, but in the peritoneum, the high mannuronic acid alginate capsules provoked the weakest response, and this type of capsule will be used for future transplantation work [14].

Associations of D-Mannuronate with other chemical compounds

• Cell growth in high guluronic acid alginate took place at random locations throughout the solid bead and not in the periphery, as was the case in high mannuronic acid alginate preparations [3].
• Capsules with an inhomogeneous solid gel core were made of alginates with high guluronic or high mannuronic acid content and poly-L (PLL)- or poly-D-lysine (PDL) of concentrations varied from 0.05-0.2% [15].

Gene context of D-Mannuronate

• An algG-deletion mutant was constructed and found to produce predominantly a dimer containing a 4-deoxy-L-erythro-hex-4-enepyranosyluronate residue at the nonreducing end and a mannuronic acid residue at the reducing end [16].
• The authors earlier demonstrated that alginates enriched in mannuronic acid stimulate human monocytes to produce high levels of cytokines such as tumour necrosis factor (TNF), IL-1 IL-6 [17].
• In the present study, we demonstrate that high mannuronic acid-containing alginate (HMA) inhibits gammaIR induced expression of ICAM-1, VCAM-1, and E-selectin on HUVEC in a dose dependent manner [18].

Analytical, diagnostic and therapeutic context of D-Mannuronate

• High mannuronic acid alginate capsules are of particular practical interest for cell transplantation and for biohybrid organs, because mannuronate-rich alginates are usually less viscous, allowing one to make gels with a higher alginate content [19].
• HPLC analysis of the degradation products of oligomannuronates and oligoalginates suggested that the beta-elimination requires the interaction of the enzyme with at least three sequential mannuronic acid residues [20].
• The mannuronic acid to guluronic acid (MG) ratio and the distribution of uronic acid residues of five sodium alginate samples have been measured using circular dichroism and NMR, with circular dichroism yielding MG ratios between 42.1 and 63.6%, depending on the grade of alginate used [21].
• RESULTS: The mannuronic acid-to-glucuronic acid ratio of viscous injectable pure alginate sol, as determined by nuclear magnetic resonance studies, was 1.2, and its viscosity at 5 percent was 17,800 mPa [22].

References