Oxidized Cellulose Binding to Allergens with a Carbohydrate-Binding Module Attenuates Allergic Reactions

Abstract

Grass and mite allergens are of the main causes of allergy and asthma. A carbohydrate-binding module (CBM) represents a common motif to groups I (β-expansin) and II/III (expansin-like) grass allergens and is suggested to mediate allergen-IgE binding. House dust mite group II allergen (Der p 2 and Der f 2) structures bear strong similarity to expansin's CBM, suggesting their ability to bind carbohydrates. Thus, this study proposes the design of a carbohydrate-based treatment in which allergen binding to carbohydrate particles will promote allergen airway clearance and prevent allergic reactions. The aim of the study was to identify a polysaccharide with high allergen-binding capacities and to explore its ability to prevent allergy. Oxidized cellulose (OC) demonstrated allergen-binding capacities toward grass and mite allergens that surpassed those of any other polysaccharide examined in this study. Furthermore, inhalant preparations of OC microparticles attenuated allergic lung inflammation in rye grass-sensitized Brown Norway rats and OVA-sensitized BALB/c mice. Fluorescently labeled OC efficiently cleared from the mouse airways and body organs. Moreover, long-term administration of OC inhalant to Wistar rats did not result in toxicity. In conclusion, many allergens, such as grass and dust mite, contain a common CBM motif. OC demonstrates a strong and relatively specific allergen-binding capacity to CBM-containing allergens. OC's ability to attenuate allergic inflammation, together with its documented safety record, forms a firm basis for its application as an alternative treatment for prevention and relief of allergy and asthma.

Helminth Allergens, Parasite-Specific IgE, and Its Protective Role in Human Immunity

“…However, this assessment is made on sequence alignment and it is possible that these plant proteins share conformational motifs formed by non-homologous sequences (mimetopes) in un-related proteins from metazoan parasites. There is some evidence for this in that the plant expansin Php p 1 has no sequence homology with the mite allergen Der p 2, but Phl p 1, and Der p 2 have domains that share function (carbohydrate-binding) and close 3D conformational homology (97). While dust-mites are not metazoan parasites, they have close relatives that are (e.g., the scabies mite, Sarcoptes scabiei ).…”

Allergen Ligands in the Initiation of Allergic Sensitization

“…Oxidised cellulose binds proteins without carbohydrate binding domains via polyuronic acid carboxylic groups and, as found for Der p 2 [99], the highest binding is found with preparations with the highest carboxylic content [100]. Indeed oxidized cellulose bound all detectable the proteins in HDM extracts [99]. It is likely, that as discussed for ML-domain proteins, the carbohydrate bound by Der p 2 will be glycolipid.…”

“…A carbohydrate binding domain was been implicated in the binding oxidised cellulose particles by Der p 2 [99] but while this ML-domain protein has a β-fold it does not have surface grooves and exposed aromatic residues. Oxidised cellulose binds proteins without carbohydrate binding domains via polyuronic acid carboxylic groups and, as found for Der p 2 [99], the highest binding is found with preparations with the highest carboxylic content [100]. Indeed oxidized cellulose bound all detectable the proteins in HDM extracts [99].…”

Comparisons of Allergenic and Metazoan Parasite Proteins: Allergy the Price of Immunity

“…Noteworthy, but scarce, examples of studies establishing structure based homology between parasite and allergenic proteins (e.g. dust mite group II allergen, Der p 2 and Der f 2 sharing structure based homology with carbohydrate-binding module of grass allergen expansin proteins) provide modest support to our hypothesis [ 35 ].…”