Differences in susceptibility to German cockroach frass and its associated proteases in induced allergic inflammation in mice

Page, Kristen; Lierl, Kristin M.; Herman, Nancy; Wills‐Karp, Marsha

doi:10.1186/1465-9921-8-91

Cited by 34 publications

(43 citation statements)

References 26 publications

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“…Cockroach frass already has been used for mucosal sensitization (37,38), although in those studies frass was administered intratracheally whereas we administered i.n. cockroach allergens.…”

Section: Discussionmentioning

confidence: 99%

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Mucosal Allergic Sensitization to Cockroach Allergens Is Dependent on Proteinase Activity and Proteinase-Activated Receptor-2 Activation

Arizmendi

Abel

Mihara

et al. 2011

The Journal of Immunology

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We have shown that proteinase-activated receptor-2 (PAR2) activation in the airways leads to allergic sensitization to concomitantly inhaled Ags, thus implicating PAR2 in the pathogenesis of asthma. Many aeroallergens with proteinase activity activate PAR2. To study the role of PAR2 in allergic sensitization to aeroallergens, we developed a murine model of mucosal sensitization to cockroach proteins. We hypothesized that PAR2 activation in the airways by natural allergens with serine proteinase activity plays an important role in allergic sensitization. Cockroach extract (CE) was administered to BALB/c mice intranasally on five consecutive days (sensitization phase) and a week later for four more days (challenge phase). Airway hyperresponsiveness (AHR) and allergic airway inflammation were assessed after the last challenge. To study the role of PAR2, mice were exposed intranasally to a receptor-blocking anti-PAR2 Ab before each administration of CE during the sensitization phase. Mucosal exposure to CE induced eosinophilic airway inflammation, AHR, and cockroach-specific IgG1. Heat-inactivated or soybean trypsin inhibitor-treated CE failed to induce these effects, indicating that proteinase activity plays an important role. The use of an anti-PAR2 blocking Ab during the sensitization phase completely inhibited airway inflammation and also decreased AHR and the production of cockroach-specific IgG1. PAR2 activation by CE acts as an adjuvant for allergic sensitization even in the absence of functional TLR4. We conclude that CE induces PAR2-dependent allergic airway sensitization in a mouse model of allergic airway inflammation. PAR2 activation may be a general mechanism used by aeroallergens to induce allergic sensitization.

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“…Cockroach frass already has been used for mucosal sensitization (37,38), although in those studies frass was administered intratracheally whereas we administered i.n. cockroach allergens.…”

Section: Discussionmentioning

confidence: 99%

“…The role of proteinase activity in the development of allergic sensitization has been shown for cockroach frass (37), house dust mite (39), pollen, and fungal proteinases (4,40), but the exact mechanisms of this effect were not studied. Our data indicate that PAR 2 activation by cockroach allergens may be the mechanism.…”

Section: Discussionmentioning

confidence: 99%

Mucosal Allergic Sensitization to Cockroach Allergens Is Dependent on Proteinase Activity and Proteinase-Activated Receptor-2 Activation

Arizmendi

Abel

Mihara

et al. 2011

The Journal of Immunology

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“…İlaveten, Alman hamamböceği frass (dışkı artıkları)'ında bulunan proteazlar hava yolunda promatrix metalloproteinase-9'ı aktive eder (20). PAR-2 eksik farede yapılan deneylerde frass proteazının havayolu enflamasyonunun indüklenmesinde rolü olduğu gösterilmiştir (21).…”

Section: Hamamböceği Allerjeni-havayolu Enflamasyonuunclassified

Cockroach Allergy and Its Immunotherapy

Özdemir

Aydın

2016

Asthma Allergy Immunol

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ÖZHamamböceği allerjisi 30 yılı aşkın süredir, solunum yolu allerjik hastalıklarının önemli bir nedeni olarak düşünülmektedir. En sık evcil hamamböceği türleri Alman (Blattella germanica) ve Amerikan (Periplaneta americana) hamamböcekleridir. Alman hamamböceği küçük, 16 mm boyunda, tüm dünyada evlerde bulunan bir böcektir. Amerikan hamamböceği daha büyük, 35-53 mm boyutunda, ev, hastane, okul ve diğer büyük binalarda da bulunabilen bir böcektir. Türkiye' de 20' den fazla hamamböceği türü olmasına rağmen, en sık Alman hamamböceğine rastlanır. ABD' de çocuk ve erişkinleri içeren değişik araştırmalarda hamamböceği allerjisi %17-41 arasında bulunmuştur. Avrupa' da allerji kliniğine başvuran çocuk ve erişkinlerde yapılan çalışmalarda ise, %4-26 oranında saptanmıştır. Türkiye' de hamamböceği allerjisi prevalansı çocuk ve erişkinleri içeren değişik araştırmalarda %2.2-51.4 arasında bildirilmiştir. Tropomyosin, Bla g7 ve Per a7 denilen, hamamböceklerindeki major allerjenlerden biridir. Ayrıca tropomyosin, böceklerle omurgasızlar (akar, kabuklular, yumuşakca ve parazitler) arasındaki çapraz reaktivitede rol oynayan bir allerjendir. Hamamböceğine duyarlı kişilerde, diğer omurgasızların allerjenlerine kosensitizasyon yaygın bir özelliktir. Böylece, parazit enfestasyonları çapraz reaktif antikorlar aracılığıyla allerjik reaktiviteyi regüle ederler. Hamamböceği allerjen düzeyini tamamen başarılı bir temizlikten sonrası bile sürekli düşük tutmak zor olmasına ilaveten, hamamböceği allerjisinin teşhis ve tedavisinde kullanılan ticari ekstraktlar standardize değildirler. Bazı çalışmalar hamamböceğine karşı immünoterapinin etkili olduğunu düşündürmesine rağmen; kaliteli ekstraktlar, daha çok sayıda ve daha uzun süre takip edilen hastalar ile yapılacak randomize kontrollü çalışmalar bu tedavinin etkinlik ve güvenilirliğini göstermek için gereklidir. ABSTRACTCockroach allergy has been considered as an important cause of respiratory allergic diseases for over three decades. The most common domiciliary cockroach species are Blattella germanica (German cockroach) and Periplaneta americana (American cockroach). Blattella germanica is a small cockroach, approximately 16 mm in length, which commonly infests houses worldwide. Periplaneta americana is a large cockroach, approximately 35-53 mm in length, that infests houses, schools, hospitals, and other large buildings. There are more than 20 different cockroach species in Turkey, and Blattella germanica is known as the most common. In the United States, the prevalence of cockroach allergy ranges from 17 to 41%'in various studies involving both children and adults. European studies on children and adults attending an allergy clinic show a high variability in cockroach sensitisation varying from %4-26. In Turkey, cockroach allergy prevalence rate varies from %2.2-51.4 in different studies consisting of both children and adults. Tropomyosin, designated as Bla g7 and Per a7, has been identified as a major allergen in cockroaches. Tropomyosin is also an important allergen involved in cross-rea...

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“…Mice were anesthetized with ketamine (45 mg/kg)/xylazine (8 mg/kg) prior to PBS or GC frass (40 µg/40 µl) exposure by a single inhalation as described previously [20,21,22]. Mice were given a lethal dose of sodium pentobarbital 1–3 h later.…”

Section: Methodsmentioning

confidence: 99%

Dendritic Cell-Derived Tumor Necrosis Factor α Modifies Airway Epithelial Cell Responses

Lutfi

Ledford²,

Zhou³

et al. 2012

J Innate Immun

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Mucosal dendritic cells (DC) are intimately associated with the airway epithelium and thus are ideally situated to be first responders to pathogens. We hypothesize that DC drive innate immune responses through early release of tumor necrosis factor (TNF) α, which drives airway epithelial cell responses. In a mouse model, TNFα release was significantly increased following a single exposure to German cockroach (GC) frass, an event independent of neutrophil recruitment into the airways. While lung epithelial cells and alveolar macrophages failed to release TNFα following GC frass exposure, bone marrow-derived DC (BMDC) produced substantial amounts of TNFα suggesting their importance as early responding cells. This was confirmed by flow cytometry of pulmonary myeloid DC. Addition of GC frass-pulsed BMDC or conditioned media from GC frass-pulsed BMDC to primary mouse tracheal epithelial cells (MTEC) or MLE-15 cells induced chemokine (C-C) motif ligand (CCL) 20 and granulocyte macrophage (GM) colony-stimulating factor (CSF), both of which are important for DC recruitment, survival and differentiation. Importantly, DC do not produce CCL20 or GM-CSF following allergen exposure. Blocking TNFα receptor 1 (TNFR1) completely abolished chemokine production, suggesting that BMDC-derived TNFα induced airway epithelial cell activation and enhancement of the innate immune response. Lastly, blocking TNFR1 in vivo resulted in significantly decreased CCL20 and GM-CSF production in the lungs of mice. Together, our data strongly suggest that DC-derived TNFα plays a crucial role in the initiation of innate immune responses through the modification of airway epithelial cell responses.

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Differences in susceptibility to German cockroach frass and its associated proteases in induced allergic inflammation in mice

Abstract: Background: Cockroach exposure is a major risk factor for the development of asthma. Inhalation of fecal remnants (frass) is the likely sensitizing agent; however isolated frass has not been tested for its ability to induce experimental asthma in mice.

Cited by 34 publications

References 26 publications

Mucosal Allergic Sensitization to Cockroach Allergens Is Dependent on Proteinase Activity and Proteinase-Activated Receptor-2 Activation

Mucosal Allergic Sensitization to Cockroach Allergens Is Dependent on Proteinase Activity and Proteinase-Activated Receptor-2 Activation

Cockroach Allergy and Its Immunotherapy

Dendritic Cell-Derived Tumor Necrosis Factor α Modifies Airway Epithelial Cell Responses

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