Inhaled aerosolized nicotine suppresses the lung eosinophilic response to house dust mite allergen.

Nicotine of unprecedented concentrations and purity is being inhaled by those using commercially available electronic nicotine delivery systems (ENDS). The consequences of this route of self-administration on the immunological response to inhaled allergens are not known. In mice, sensitization and inhalation challenge with the common environmental house dust mite (HDM) allergen is an experimental model of this response. When mice were exposed to aerosolized nicotine base (aeroNic) twice daily, 5 days/wk for 8 wk, the HDM-induced recruitment of eosinophils (EOS) was substantially reduced as measured in bronchial alveolar lavage fluid (BALF). Oral nicotine administration had no effect. HDM challenge in the presence of nicotinic receptor subtype α7 (α7)-specific type-1 positive allosteric modulators (PAMs) was alone sufficient to suppress EOS. RNA analysis of alveolar macrophages (AM) collected from BALF after HDM challenge of aeroNic revealed that α7 activation strongly suppresses initiation of Ccl24 (eotaxin 2) transcription. To examine possible cellular signaling mechanisms coupling α7 to Ccl24 transcription, an AM culture model system was used. In AM cultures of freshly collected BALF, Ccl24 transcription was robustly activated by a mixture of IL-4 and IL-10, and this was suppressed by coapplication of type-1 PAMs through a pathway that requires p38MAPK but is independent of Jak2. These results suggest that the EOS response to HDM inhaled allergen is subject to modulation through activation of the α7 receptor and suggest that the allergic response may be substantially modified in ENDS users.

Sequence polymorphisms of Der f 1, Der p 1, Der f 2 and Der p 2 from Korean house dust mite isolates.

Amino acid sequence variations have possible influences on the allergenicity of allergens and may be important factors in allergen standardization. This study was undertaken to investigate the sequence polymorphisms of group 1 and 2 allergens from Korean isolates of the house dust mites Dermatophagoides farinae and D. pteronyssinus. cDNA sequences encoding group 1 and 2 allergens were amplified by RT-PCR and compared the deduced amino acid sequences. Der f 1.0101, which appeared in 64.0 % of the 50 sequences analyzed, was found to be predominant. Among the Der p 1 sequences, Der p 1.0102 and 1.0105 were predominant (58 %). Among the Der f 2 sequences, Der f 2.0102 (40.7 %) and a new variant with Gly at position 42 (27.8 %) were predominant. The deduced amino acid sequences of 60 Der p 2 clones were examined, and 28 variants with 1-5 amino acid substitutions were found. Interestingly, all of the Der p 2 sequences had Thr instead of Lys at position 49. Two variants (Leu40, Thr49, and Asn114 (26.6 %); Val40, Thr49, and Asn114 (20.0 %)) were found to be the most predominant forms of Der p 2. Der p 1 has a high rate of sporadic substitutions and the group 2 allergens show a more regular pattern with orderly associations of amino acid substitutions. Der f 1 and Der p 2 from Korean mite isolates have unique amino acid sequence polymorphisms. These findings provide important data for house dust mite allergen standardization.

House dust mite allergen Der f 1 can induce the activation of latent TGF-beta via its protease activity.

A major house dust mite allergen Der f 1 belongs to the papain-like cysteine protease family. This study investigated whether Der f 1 can cleave the latency-associated peptide (LAP) of transforming growth factor (TGF)-beta via its proteolytic activity and activate latent TGF-beta. We found that Der f 1 can cleave LAP and induce the activation of latent TGF-beta, leading to functional Smad signaling. Importantly, these actions of Der f 1 were inhibited by cysteine protease inhibitor E64 or inactivation of the protease activity by heat. Thus, latent TGF-beta may be a direct target of Der f 1 protease activity.

Reduction of house-dust mite allergen concentrations in carpets by aluminium potassium sulfate dodecahydrate (alum).

Special tools and skilled labor are required to reduce house-dust mite allergens in carpets. The main house-dust mite allergen is Der p 1, a soluble protein found in high abundance in woolen carpets. Current chemical treatment options are either unsafe or ineffective in eradicating Der p 1. Here, we present an effective, safe, and easy application reagent to reduce the allergen levels in carpets. Sixty woolen carpets with Der p 1 concentrations >2 microg/g in fine dust were divided into three homogeneous groups of 20 carpets each, according to their allergen load. We tested alum dissolved in 60 mL of water at doses of 3, 6, and 9 g/m2 against Der p 1 in groups 1, 2, and 3, respectively. The test side of the carpets was sprayed with the reagent. The control side was treated with the 60 mL of tap water. Dust particles were collected from a 1-m2 area on each carpet side 24 hours after treatment and were analyzed for Der p 1 content with a monoclonal ELISA. Alum reduced the Der p 1 concentrations by 48.6 +/- 6.2%, 78.8 +/- 7.2%, and 95.2 +/- 3.0% at 3, 6, and 9 g/m2 in the carpets, respectively. Moreover, there were no complaints registered by the residents against the alum applications. Alum, at 9 g/m2 (in a solution at 15%) in water, can be used for decreasing existing Der p 1 concentrations in woolen carpets.

Placebo-controlled study of the mite allergen-reducing effect of tannic acid plus benzyl benzoate on carpets in homes of children with house dust mite sensitization and asthma.

We studied the effect of a spray containing 1% benzyl benzoate, an acaricide, and 1% tannic acid ('Lowal'; a protein-denaturing substance), on concentrations of major allergens from house dust mite (HDM) species Dermatophagoides pteronyssinus and D. farinae (Der p 1 and Der f 1, respectively) in carpets. In a double-blind, placebo-controlled study with crossover design, 30 homes of children with HDM sensitization and asthma were included. All houses showed > or = 400 ng/g of Der p 1 + Der f 1 in carpet dust. The first treatment was performed on day 0 (group 1 active treatment, n = 15; group 2 placebo treatment, n = 15). After 2 and 8 weeks, dust samples were collected for quantification of mite allergens. After a 2-week washout period, the second treatment was performed (group 1 placebo treatment; group 2 active treatment). Again, carpet dust was collected after 2 and 8 weeks. Twenty-two of 30 families completed the trial: 14/15 in group 1 and eight of 15 in group 2. On day 0, there was no significant difference in mite allergen exposure between group 1 and group 2 (1,498 vs. 2,239 ng/g of Der p 1 + Der f 1, respectively). In group 1, the geometric mean for the difference of mite allergen concentration comparing day 0 and week 6 was 196 ng/g (95% CI: -7,161 and 8,401) for the first treatment (active) and 15 ng/g (95% CI: -1,079 and 1,292) for the second treatment (control). In group 2, the difference was 66 ng/g (95% CI: -398 and 1,515) for the first treatment (control) and 609 ng/g (95% CI: 186 and 9,264) for the second treatment (active). Comparing placebo and active treatment in total, there was a significant decrease following placebo treatment after 14 days (p = 0.026). After 8 weeks, active treatment was superior to placebo treatment (p = 0.049), but the allergen reduction achieved was < 20% (median 1,500 ng/g on day 0 vs. 1,250 ng/g after 8 weeks). We conclude that the slight mite allergen reduction on carpets achieved by the treatment with 'Lowal' is unlikely to achieve worthwhile clinical benefit either in the treatment of mite-sensitive patients or in primary or secondary prophylaxis.