Protein and Antibody Engineering: Suppressing Degranulation of the Mast Cells and Type I Hypersensitivity Reaction

2020 ◽  
Vol 21 (8) ◽  
pp. 831-841
Author(s):  
Huda Fatima Rajani ◽  
Solmaz Shahidi ◽  
Mohammad Mahmoudi Gomari

With an increase in atopic cases and owing to a significant role of mast cells in type I hypersensitivity, a therapeutic need to inhibit degranulation of mast cells has risen. Mast cells are notorious for IgE-mediated allergic response. Advancements have allowed researchers to improve clinical outcomes of already available therapies. Engineered peptides and antibodies can be easily manipulated to attain desired characteristics as per the biological environment. A number of these molecules are designed to target mast cells in order to regulate the release of histamine and other mediators, thereby controlling type I hypersensitivity response. The aim of this review paper is to highlight some of the significant molecules designed for the purpose.

2009 ◽  
Vol 77 (9) ◽  
pp. 1506-1512 ◽  
Author(s):  
Jie Wan Kim ◽  
Jun Ho Lee ◽  
Bang Yeon Hwang ◽  
Se Hwan Mun ◽  
Na Young Ko ◽  
...  

2015 ◽  
Vol 84 (2015) (09) ◽  
pp. 138-144 ◽  
Author(s):  
Ladan Zand ◽  
Myles Monaghan ◽  
Benjamin R. Griffin ◽  
Steven J. Wagner ◽  
Iasmina M. Criaci ◽  
...  

Anaphylaxis 110 Anaphylactic reactions (type I hypersensitivity reaction) are the consequence of the cascade caused by an IgE-mediated response to a specific antigen. Prior exposure to the antigen sensitizes the individual, so that subsequent exposure results in prostaglandin, leukotriene, and platelet activating factor generation and thereby histamine release. This results in vasodilatation, bronchial mucosal oedema, and bronchoconstriction....


1997 ◽  
Vol 25 (01) ◽  
pp. 51-56 ◽  
Author(s):  
Young Mi Lee ◽  
Chang Young Kim ◽  
Youn Chul Kim ◽  
Hyung Min Kim

A study was carried out to examine the effect of an aqueous extract from immature fruit of Poncirus trifoliata L. (Rutaceae) (PTIFE) on the type I hypersensitivity reaction. Forty-eight hour PCA (passive cutaneous anaphylaxis) in rats was significantly inhibited by the oral administration of PTIFE (200 mg/kg). It also inhibited histamine release from rat peritoneal mast cells (RPMC) induced by mouse anti-dinitrophenyl (DNP)-lgE and dinitrophenyl-human serum albumin (DNP-HSA). These results suggest that PTIFE has anti-allergic action against the type I hypersensitivity reaction.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Matteo Borro ◽  
Simone Negrini ◽  
Andrew Long ◽  
Sharon Chinthrajah ◽  
Giuseppe Murdaca

AbstractHistamine is a monoamine synthesized from the amino acid histidine that is well-known for its role in IgE-mediated anaphylaxis but has shown pleiotropic effects on the immune system, especially in order to promote inflammatory responses. H1-receptor antagonist are common drugs used in mild/moderate allergic reactions whereas H2-receptor antagonist are commonly administered in gastric ulcer but showed some properties in allergy too. The EAACI guidelines for diagnosis and treatment of anaphylactic reactions recommend their use as third-line therapy in adjunct to H1-antagonists. The purpose of this article is to produce a complete summary of findings and evidence known so far about the usefulness of H2-receptor antagonist in allergic reactons.


2021 ◽  
Vol 55 (1) ◽  
pp. 54
Author(s):  
Nur Moya Isyroqiyyah ◽  
Gatot Soegiarto ◽  
Yuani Setiawati

Drug hypersensitivity is defined as an untoward response to medication which is noxious and unintended, and which occurs at doses normally used in human either for the prophylaxis, diagnosis, or therapy of disease or for the modification of physiological function. Drug hypersensitivity is common and may cause emergency condition until death. The incidence of drug hypersensitivity-related hospitalizations has usually been assessed within hospitals. The aim of this study is to determine the profile of drug hypersensitivity patients hospitalized at Dr. Soetomo Hospital in 6 months period from January to June 2016. This study was a descriptive retrospective study on medical records of drug hypersensitivity patients hospitalized in Dr. Soetomo Hospital in 6 months period. The patient’s demographic data, the type of hypersensitivity reaction, and the final outcome of the hospitalization were collected. Within the 6 months period, there were 16 drug hypersensitivity patients hospitalized in Dr. Soetomo Hospital. Most of them are female (56.25%), and aged between 46-55 years (25%). There were 4 patients (25%) with type I hypersensitivity: urticaria, angioedema and anaphylaxis; while type IV hypersensitivity occured in 12 patients (75%): Stevens-Johnson syndrome, Stevens-Johnson syndrome-Toxic Epidermal Necrolysis overlap, erythroderma, maculopapular drug eruptions, and DRESS. Most of the patients (87.5%) had favorable outcome after hospitalization. There were 16 patients with drug hypersensitivity reaction hospitalized in Dr. Soetomo Hospital, Surabaya in 6 months period. Most of them were female and had type IV hypersensitivity reactions.


2021 ◽  
Vol 30 (3) ◽  
pp. 111-117
Author(s):  
Ghada A. Mokhtar ◽  
Sylvia W. Roman ◽  
Aya M. Elgendy ◽  
Marian A. Gerges ◽  
Alsayed Abdulmageed ◽  
...  

Background: Allergic fungal rhinosinusitis (AFRS) is a distinct form of chronic rhinosinusitis. Type I hypersensitivity to inhaled fungal allergens has been implicated as key pathogenesis. Immunotherapy as one of the therapeutic options is still controversial. Objective: to evaluate the role of immunotherapy in the management of AFRS patients not responding to medical treatment 3 months following endoscopic surgery. Methodology: A total of 35 patients diagnosed as resistant AFRS were included in this prospective study. Patients were diagnosed following clinical, radiological, and endoscopic examination of nose and paranasal sinuses. Specimens were collected during endoscopy and subjected to microscopic examination and fungal culture. Skin prick test and assessment of total IgE level were performed for all patients. Sublingual immunotherapy (SLIT) was initiated for all patients for 6 months. Clinical efficacy of SLIT was assessed using the 20-item sino-nasal outcome test (SNOT-20) score. Results: Aspergillus spp. was the most frequent fungus isolated (74.3%) from patients. All patients were sensitized to mixed fungi. Elevated total IgE (> 100 IU/mL) was found in all patients with 40% of them had peripheral eosinophilia. A significant improvement (p < 0.001) was recorded in the SNOT-20 score of examined patients recording a mean of 1.2 ± 0.3, 6 months after SLIT compared to 1.93 ± 0.44 before immunotherapy initiation. Conclusion: Immunotherapy appears to be a good adjunctive therapy for the management of resistant cases of AFRS.


2020 ◽  
Vol 21 (4) ◽  
pp. 1498 ◽  
Author(s):  
David O. Lyons ◽  
Nicholas A. Pullen

Mast cells are often regarded through the lens of IgE-dependent reactions as a cell specialized only for anti-parasitic and type I hypersensitive responses. However, recently many researchers have begun to appreciate the expansive repertoire of stimuli that mast cells can respond to. After the characterization of the interleukin (IL)-33/suppression of tumorigenicity 2 (ST2) axis of mast cell activation—a pathway that is independent of the adaptive immune system—researchers are revisiting other stimuli to induce mast cell activation and/or subsequent degranulation independent of IgE. This discovery also underscores that mast cells act as important mediators in maintaining body wide homeostasis, especially through barrier defense, and can thus be the source of disease as well. Particularly in the gut, inflammatory bowel diseases (Crohn’s disease, ulcerative colitis, etc.) are characterized with enhanced mast cell activity in the context of autoimmune disease. Mast cells show phenotypic differences based on tissue residency, which could manifest as different receptor expression profiles, allowing for unique mast cell responses (both IgE and non-IgE mediated) across varying tissues as well. This variety in receptor expression suggests mast cells respond differently, such as in the gut where immunosuppressive IL-10 stimulates the development of food allergy or in the lungs where transforming growth factor-β1 (TGF-β1) can enhance mast cell IL-6 production. Such differences in receptor expression illustrate the truly diverse effector capabilities of mast cells, and careful consideration must be given toward the phenotype of mast cells observed in vitro. Given mast cells’ ubiquitous tissue presence and their capability to respond to a broad spectrum of non-IgE stimuli, it is expected that mast cells may also contribute to the progression of autoimmune disorders and other disease states such as metastatic cancer through promoting chronic inflammation in the local tissue microenvironment and ultimately polarizing toward a unique Th17 immune response. Furthermore, these interconnected, atypical activation pathways may crosstalk with IgE-mediated signaling differently across disorders such as parasitism, food allergies, and autoimmune disorders of the gut. In this review, we summarize recent research into familiar and novel pathways of mast cells activation and draw connections to clinical human disease.


Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2131 ◽  
Author(s):  
Dong Eun Kim ◽  
Kyoung-jin Min ◽  
Min-Jong Kim ◽  
Sang-Hyun Kim ◽  
Taeg Kyu Kwon

Hispidulin (4′,5,7-trihydroxy-6-methoxyflavone) is a natural compound derived from traditional Chinese medicinal herbs, and it is known to have an anti-inflammatory effect. Here, we investigated the effect of hispidulin on the immunoglobulin E (IgE)-mediated allergic responses in rat basophilic leukemia (RBL)-2H3 mast cells. When RBL-2H3 cells were sensitized with anti-dinitrophenyl (anti-DNP) IgE and subsequently stimulated with DNP-human serum albumin (HSA), histamine and β-hexosaminidase were released from the cells by degranulation of activated mast cells. However, pretreatment with hispidulin before the stimulation of DNP-HSA markedly attenuated release of both in anti-DNP IgE-sensitized cells. Furthermore, we investigated whether hispidulin inhibits anti-DNP IgE and DNP-HSA-induced passive cutaneous anaphylaxis (PCA), as an animal model for Type I allergies. Hispidulin markedly decreased the PCA reaction and allergic edema of ears in mice. In addition, activated RBL-2H3 cells induced the expression of inflammatory cytokines (tumor necrosis factor-α and interleukin-4), which are critical for the pathogenesis of allergic disease, through the activation of c-Jun N-terminal kinase (JNK). Inhibition of JNK activation by hispidulin treatment reduced the induction of cytokine expression in the activated mast cells. Our results indicate that hispidulin might be a possible therapeutic candidate for allergic inflammatory diseases through the suppression of degranulation and inflammatory cytokines expression.


Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2172-2180 ◽  
Author(s):  
Kotaro Suzuki ◽  
Hiroshi Nakajima ◽  
Norihiko Watanabe ◽  
Shin-ichiro Kagami ◽  
Akira Suto ◽  
...  

Abstract The regulatory roles of the common cytokine receptor γ chain (γc)– and Jak3-dependent signaling in the proliferation and survival of mast cells were determined using γc-deficient (γc−) and Jak3-deficient (Jak3−) mice. Although the mast cells in γc− and Jak3− mice were morphologically indistinguishable from those in wild-type mice, the number of peritoneal mast cells was decreased in γc− and Jak3− mice as compared with that in wild-type mice. Among γc-related cytokines, interleukin (IL)-4 and IL-9, but not IL-2, IL-7, or IL-15, enhanced the proliferation and survival of bone marrow–derived mast cells (BMMCs) from wild-type mice. However, the effects of IL-4 and IL-9 were absent in BMMCs from γc− and Jak3−mice. In addition, IL-4Rα, γc, and Jak3, but not IL-2Rβ or IL-7Rα, were expressed in BMMCs. In contrast, IL-13 did not significantly induce the proliferation and survival of BMMCs even from wild-type mice, and IL-13Rα1 was not expressed in BMMCs. Furthermore, IL-4 phosphorylated the 65-kd isoform of Stat6 in BMMCs from wild-type mice but not from γc− and Jak3− mice. These results indicate that γc- and Jak3-dependent signaling is essential for IL-4– and IL-9–induced proliferation and survival of murine mast cells, that the effects of IL-4 are mediated by type I IL-4R and that type II IL-4R is absent on mast cells, and that IL-4 phosphorylates the 65-kd isoform of Stat6 in mast cells in a γc- and Jak3-dependent manner.


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