Experimental Modeling of Eosinophil-Associated Diseases.

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This chapter reviews eosinophil involvement in inflammatory diseases including EGID, asthma, and pancreatic disorders, highlighting the need for further research into eosinophil-targeting treatments.

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This chapter reviews eosinophil biology and experimental disease models, focusing on eosinophil degranulation and the toxic granule proteins MBP, ECP, EPO, and EDN across eosinophilic gastrointestinal disorders (EGID), asthma, hypereosinophilic syndrome, eosinophilic pneumonia, and eosinophil-associated pancreatic disorders. It synthesizes reported evidence of eosinophil presence in acute, recurrent acute, and chronic pancreatitis and pancreatic cancer, while also summarizing known animal-model approaches for eosinophil-driven airway and gut inflammation and related signaling pathways (e.g., IL-5/IL-13/IL-15). A stated limitation is that the detailed patterns of eosinophil accumulation during pancreatic diseases are not well explored, necessitating further preclinical and clinical work. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Eosinophils are an important subtype of leukocytes derived from bone marrow multipotent hematopoietic stem cells and represent about 1% of leukocytes in circulating blood. In homeostatic conditions, eosinophils reside in the intestine to maintain the balance of immune responses by communicating with gut microbes without causing inflammation. However, under the stressed or diseased condition, eosinophils degranulate, releasing their granule-derived cytotoxic proteins that are involved in inflammatory responses. Various eosinophil-associated inflammatory diseases are eosinophilic esophagitis (EoE), eosinophilic gastroenteritis (EG), and eosinophilic colitis (EC), together called EGID, asthma, hypereosinophilic syndrome, and eosinophilic pneumonia (EP). Eosinophil degranulation results in the release of their four toxic proteins [major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin (EDN)] which promote disease pathogenesis. Pancreatitis is the inflammatory disease of the pancreas that arises due to blockage of the pancreatic duct, trypsinogen mutation, alcohol consumption, and repeated occurrence of pancreatitis leading to chronic pancreatitis (CP); subsequently some CP patients may also develop pancreatic cancer. The presence of eosinophils is now shown in various case reports with acute, recurrent acute, and chronic pancreatitis and pancreatic cancer indicating the role of eosinophils in the pathogenesis of various pancreatic inflammatory disorders. However, the details of eosinophil accumulation during pancreatic diseases are not well explored and need further attention. Overall, the chapter provides the current understanding of reported eosinophils associated with inflammatory diseases like EGID diseases, asthma, and pancreatic disorders, i.e., acute, chronic pancreatitis, and pancreatic cancer. This knowledge will be helpful for future studies to develop novel treatment options for the eosinophils associated diseases. Therefore, more efforts are needed to perform preclinical and clinical studies in this field for the successful development of eosinophil-targeting treatments for a variety of eosinophil-associated diseases.
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Abstract

Eosinophils are an important subtype of leukocytes derived from bone marrow multipotent hematopoietic stem cells and represent about 1% of leukocytes in circulating blood. In homeostatic conditions, eosinophils reside in the intestine to maintain the balance of immune responses by communicating with gut microbes without causing inflammation. However, under the stressed or diseased condition, eosinophils degranulate, releasing their granule-derived cytotoxic proteins that are involved in inflammatory responses. Various eosinophil-associated inflammatory diseases are eosinophilic esophagitis (EoE), eosinophilic gastroenteritis (EG), and eosinophilic colitis (EC), together called EGID, asthma, hypereosinophilic syndrome, and eosinophilic pneumonia (EP). Eosinophil degranulation results in the release of their four toxic proteins [major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin (EDN)] which promote disease pathogenesis. Pancreatitis is the inflammatory disease of the pancreas that arises due to blockage of the pancreatic duct, trypsinogen mutation, alcohol consumption, and repeated occurrence of pancreatitis leading to chronic pancreatitis (CP); subsequently some CP patients may also develop pancreatic cancer. The presence of eosinophils is now shown in various case reports with acute, recurrent acute, and chronic pancreatitis and pancreatic cancer indicating the role of eosinophils in the pathogenesis of various pancreatic inflammatory disorders. However, the details of eosinophil accumulation during pancreatic diseases are not well explored and need further attention. Overall, the chapter provides the current understanding of reported eosinophils associated with inflammatory diseases like EGID diseases, asthma, and pancreatic disorders, i.e., acute, chronic pancreatitis, and pancreatic cancer. This knowledge will be helpful for future studies to develop novel treatment options for the eosinophils associated diseases. Therefore, more efforts are needed to perform preclinical and clinical studies in this field for the successful development of eosinophil-targeting treatments for a variety of eosinophil-associated diseases. Access this chapter Tax calculation will be finalised at checkout Purchases are for personal use only Similar content being viewed by others

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Am J Physiol Gastroint Liver Physiol 314:G211–G222. https://doi.org/10.1152/ajpgi.00210.2017 Acknowledgments Dr. Mishra is the Endowed Schlieder Chair; therefore, the authors thank Edward G. Schlieder Educational Foundation and Tulane University Bridge funding for the help in this study. Present address for Murali. Manohar: School of Medicine, Gastrointestinal and Hepatology Division, Stanford University, CA 94304. Author information Authors and Affiliations Corresponding author Editor information Editors and Affiliations Rights and permissions Copyright information © 2021 Springer Science+Business Media, LLC, part of Springer Nature About this protocol Cite this protocol Upparahalli Venkateshaiah, S., Manohar, M., Kandikattu, H.K., Mishra, A. (2021). Experimental Modeling of Eosinophil-Associated Diseases. In: Walsh, G.M. (eds) Eosinophils. Methods in Molecular Biology, vol 2241. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1095-4_21 Download citation DOI: https://doi.org/10.1007/978-1-0716-1095-4_21 Published: Publisher Name: Humana, New York, NY Print ISBN: 978-1-0716-1094-7 Online ISBN: 978-1-0716-1095-4 eBook Packages: Springer Protocols

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