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The Role of Extracellular Cyclophili...

Stemmy, Erik Joseph.

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The Role of Extracellular Cyclophilins in Chronic Allergic Asthma.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	The Role of Extracellular Cyclophilins in Chronic Allergic Asthma./
作者:	Stemmy, Erik Joseph.
面頁冊數:	147 p.
附註:	Source: Dissertation Abstracts International, Volume: 72-05, Section: B, page: 2719.
Contained By:	Dissertation Abstracts International72-05B.
標題:	Health Sciences, Pathology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3444353
ISBN:	9781124518947

The Role of Extracellular Cyclophilins in Chronic Allergic Asthma.
Stemmy, Erik Joseph.

The Role of Extracellular Cyclophilins in Chronic Allergic Asthma. - 147 p.

Source: Dissertation Abstracts International, Volume: 72-05, Section: B, page: 2719.

Thesis (Ph.D.)--The George Washington University, 2011.

Allergic asthma is characterized by acute influxes of pro-inflammatory leukocytes in response to allergen stimulation, followed by quiescent (chronic) periods between allergen challenges in which sustained low-level inflammation is observed. These chronic phases of disease are thought to be mediated by populations of leukocytes persisting within airways and lung tissues. The mechanisms regulating these persistent leukocyte populations are unknown. While classical leukocyte-attracting chemokines are highly elevated following acute allergen challenge, in both humans and animal models they return to baseline levels within 24 h and remain close to undetectable during the chronic phase. In the current studies we investigated whether an alternative family of chemoattractants, extracellular cyclophilins, might instead play a role in regulating leukocyte recruitment and persistence during chronic asthma. We optimized and characterized a new mouse model of chronic allergic asthma, and show elevated levels of extracellular cyclophilin A, but not classical chemokines, throughout the chronic phase of asthma. Further, blocking the activity of cyclophilins during this phase reduced the number of persisting leukocytes by up to 80%. This reduction was also associated with a significant inhibition of acute disease reactivation upon subsequent allergen challenge: leukocyte infiltration was reduced by more than 60%, and this translated to profound improvements in lung function. We also investigated whether cyclophilins were present in nasal wash samples of human asthma patients in the chronic phase of disease. We observed significant increases in cyclophilin B in the asthma cohort, as well as significant associations between cyclophilins and several parameters of asthma severity.

ISBN: 9781124518947Subjects--Topical Terms:

1017854
Health Sciences, Pathology.

The Role of Extracellular Cyclophilins in Chronic Allergic Asthma.
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520 $a Allergic asthma is characterized by acute influxes of pro-inflammatory leukocytes in response to allergen stimulation, followed by quiescent (chronic) periods between allergen challenges in which sustained low-level inflammation is observed. These chronic phases of disease are thought to be mediated by populations of leukocytes persisting within airways and lung tissues. The mechanisms regulating these persistent leukocyte populations are unknown. While classical leukocyte-attracting chemokines are highly elevated following acute allergen challenge, in both humans and animal models they return to baseline levels within 24 h and remain close to undetectable during the chronic phase. In the current studies we investigated whether an alternative family of chemoattractants, extracellular cyclophilins, might instead play a role in regulating leukocyte recruitment and persistence during chronic asthma. We optimized and characterized a new mouse model of chronic allergic asthma, and show elevated levels of extracellular cyclophilin A, but not classical chemokines, throughout the chronic phase of asthma. Further, blocking the activity of cyclophilins during this phase reduced the number of persisting leukocytes by up to 80%. This reduction was also associated with a significant inhibition of acute disease reactivation upon subsequent allergen challenge: leukocyte infiltration was reduced by more than 60%, and this translated to profound improvements in lung function. We also investigated whether cyclophilins were present in nasal wash samples of human asthma patients in the chronic phase of disease. We observed significant increases in cyclophilin B in the asthma cohort, as well as significant associations between cyclophilins and several parameters of asthma severity.
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