Secretory protein beta‐lactoglobulin in cattle stable dust may contribute to the allergy‐protective farm effect

Abstract

Background Growing up on a cattle farm and consuming raw cow's milk protects against asthma and allergies. We expect a cattle‐specific protein as active component in this farm effect. Methods Dust was collected from cattle and poultry stables and from mattresses of households. Urine was obtained from cattle, and ambient aerosols were sampled. Samples were analysed for BLG by SDS PAGE/immunoblot and mass spectrometry, and for association with metals by SEC‐ICP‐MS. PBMC of healthy donors were incubated with BLG +/− zinc, and proliferation and cytokines determined. BALB/c mice were pre‐treated intranasally with stable dust extract containing BLG or depleted of BLG, and subsequent allergy response after sensitization was evaluated on antibody and symptom level. Results A major protein in dust from cattle farms and ambient air was identified as BLG. Urine from female and male cattle is a major source of BLG. In dust samples, BLG was associated with zinc. In vitro , zinc‐BLG provoked significantly lower proliferation of CD4 + and CD8 + cells while inducing significantly higher levels of IFN‐γ and IL‐6 than the apo‐BLG devoid of zinc. In vivo , pre‐treatment of mice with dust extract containing BLG resulted in lower allergy symptom scores to BLG and unrelated Bet v 1 than pre‐treatment with extract depleted of BLG. These in vitro and in vivo effects were independent of endotoxin. Conclusion The lipocalin BLG is found in large amounts in cattle urine, accumulates in bovine dust samples and is aerosolized around farms. Its association with zinc favorably shapes the human cellular immune response towards Th1‐cytokines in vitro . BLG together with zinc in stable dust protects mice from allergic sensitization. BLG with its associated ligands may in an innate manner contribute to the allergy‐protective farm effect.

Milk Whey Hydrolysates as High Value-Added Natural Polymers: Functional Properties and Applications

“…β-Lactoglobulin is not found in breast milk and is considered to be responsible for some allergic reactions in infants fed with cow milk products. For this reason, there are commercial products that imitate human milk based on whey [ 24 , 25 ]. Traditionally, β-lactoglobulin is separated by fractional precipitation with ammonium sulfate at pH with or without heating to cause the precipitation of all serum proteins other than β-lactoglobulin, which are characterized commonly by chromatographic methods such as ion exchange chromatography [ 26 ].…”

The extended farm effect: The milk protein β-lactoglobulin in stable dust protects against allergies

“…BLG was identified as a central protein in ambient air and in stable dust ( Figure 1 ). Therein, it was associated with zinc in its holo-form [ 25 ]. Urine from both female and male cattle served as the primary source of BLG.…”

“…In more detailed investigations, BLG could also be found in the dust of farm households [ 25 ], which indicates that people in the household and around the farm who do not have direct contact with stables also benefit from the protective effect.…”

“…To investigate the effect of BLG-zinc on the cellular system, PBMC of healthy donors were stimulated with BLG or BLG-zinc. BLG associated with zinc resulted in lower proliferation of CD4+ and CD8+ T cells and promoted a Th1 cytokine milieu, which ultimately counteracts allergy development [ 25 ].…”

“…The latter were also identified for the first time in the GABRIELA study as key proteins of raw milk: the proteins α-lactalbumin, β-lactoglobulin (BLG) as well as bovine serum albumin were found to reduce asthma prevalence [ 1 ]. For the protein BLG, our research group was able to show that together with its ligands like iron-siderophores, vitamin A and D, or zinc, can protect against allergic immune reactions [ 20 , 21 , 22 , 23 , 24 , 25 ].…”