Interaction of human lung surfactant proteins A and D with mite (Dermatophagoides pteronyssinus) allergens

Abstract

SUMMARYHuman lung surfactant proteins A (SP-A) and D (SP-D) are both collagenous C-type lectins which appear to mediate antimicrobial activity by binding to carbohydrates on micro-organisms and to receptors on phagocytic cells. Purified native SP-A and SP-D, isolated from human bronchoalveolar lavage fluid, were found to bind to whole mite extracts (Dermatophagoides pteronyssinus) and the purified allergen Der p I, in a carbohydrate-specific and calcium-dependent manner. Binding was inhibited by ethylenediamine tetra-acetic acid (EDTA) as well as by maltose in the case of SP-D, or mannose in the case of SP-A. A recombinant polypeptide, which trimerized to form the neck region and carbohydrate recognition domains of SP-D, also inhibited the binding of native SP-D to the whole mite extract and Der p I. Both SP-A and SP-D did not bind to deglycosylated whole mite extracts or to recombinant Der p proteins, which lacked carbohydrate residues. These results suggest that the ability of surfactant proteins to bind certain allergens is mediated through their carbohydrate-recognition domains (CRDs) interacting with carbohydrate residues on the allergens. Moreover, SP-A and SP-D were found to inhibit allergen-specific IgE binding to the mite extracts either via steric hindrance or competitive binding. It is therefore possible that SP-A and SP-D may be involved in the modulation of allergen sensitization and/or the development of allergic reactions.

Major House Dust Mite Allergens Dermatophagoides pteronyssinus 1 and Dermatophagoides farinae 1 Degrade and Inactivate Lung Surfactant Proteins A and D

“…It is plausible that many of the protective, anti-allergic effects of collectins seen in vitro and in vivo are mediated through interactions with the allergens themselves (15)(16)(17)(18)(19). To determine whether the collectins could bind to the allergens within the lung environment, solid phase binding assays were performed in BALF, which contains lipids and competitor proteins that would normally be present in the lung environment.…”

“…Previous studies have demonstrated interactions between lung collectins and Der p allergens (18), but these assays were carried out in BALF to determine whether the interactions could take place in the presence of competitor proteins and lipids that would normally be present in the lung environment. NhSP-D, NhSP-A, and rfhSP-D all bound to Der p 1 and Der f 1 in a dose-dependent manner.…”

“…The mechanisms by which SP-A and SP-D bring about these protective effects are not clearly defined but in vitro studies have shown that SP-A and SP-D bind to glycosylated Der p and A. fumigatus allergens through their CRDs in a calcium-dependent manner (18,19) with consequent inhibitory effects on allergeninduced histamine release (19,20), and furthermore, SP-A and SP-D have also been shown to inhibit allergen-induced T lymphocyte proliferation (20). These in vitro properties of SP-A and SP-D may account for some of their protective effects seen in vivo.…”

Susceptibility of Mice Genetically Deficient in the Surfactant Protein (SP)-A or SP-D Gene to Pulmonary Hypersensitivity Induced by Antigens and Allergens of Aspergillus fumigatus

“…SP-A and SP-D can bind via their lectin domains to allergenic extracts derived from pollens, the house dust mite, and Aspergillus fumigatus (Afu) inhibit specific IgE binding to allergens, and block allergen-induced histamine release from sensitized basophils (15)(16)(17). SP-A and SP-D can reduce the proliferation of PBMC isolated from mite-sensitive asthmatic children (18), and SP-D, in particular, has a suppressive effect on the secretions of IL-2 by PBMC (19).…”

Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens

“…binding of allergen-specific IgE to mite allergens (9), suggesting that these surfactant proteins may be involved in modulating allergic reactions.…”