The polymeric mucin Muc5ac is required for allergic airway hyperreactivity.
The polymeric mucin Muc5ac is required for allergic airway hyperreactivity.
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DOI：
10.1038/ncomms7281
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发表时间：
2015-02-17
影响因子：
16.6
通讯作者：
Dickey, Burton F.
中科院分区：
文献类型：
--
作者：
Evans, Christopher M.;Raclawska, Dorota S.;Ttofali, Fani;Liptzin, Deborah R.;Fletcher, Ashley A.;Harper, Daniel N.;McGing, Maggie A.;McElwee, Melissa M.;Williams, Olatunji W.;Sanchez, Elizabeth;Roy, Michelle G.;Kindrachuk, Kristen N.;Wynn, Thomas A.;Eltzschig, Holger K.;Blackburn, Michael R.;Tuvim, Michael J.;Janssen, William J.;Schwartz, David A.;Dickey, Burton F.
In asthma, airflow obstruction is thought to result primarily from inflammation-triggered airway smooth muscle (ASM) contraction. However, anti-inflammatory and smooth muscle-relaxing treatments are often temporary or ineffective. Overproduction of the mucin MUC5AC is an additional disease feature that, while strongly associated pathologically, is poorly understood functionally. Here we show that Muc5ac is a central effector of allergic inflammation that is required for airway hyperreactivity (AHR) to methacholine (MCh). In mice bred on two well-characterized strain backgrounds (C57BL/6 and BALB/c) and exposed to two separate allergic stimuli (ovalbumin and Aspergillus extract), genetic removal of Muc5ac abolishes AHR. Residual MCh responses are identical to unchallenged controls, and although inflammation remains intact, heterogeneous mucus occlusion decreases by 74%. Thus, whereas inflammatory effects on ASM alone are insufficient for AHR, Muc5ac-mediated plugging is an essential mechanism. Inhibiting MUC5AC may be effective for treating asthma and other lung diseases where it is also overproduced.
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DOI：
10.1056/nejmra0910061
发表时间：
2010-12-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Fahy JV;Dickey BF
通讯作者：
Dickey BF
影响因子：
24.3
作者：
Daviskas, E;Anderson, SD;Bautovich, G
通讯作者：
Bautovich, G
DOI：
10.1152/ajplung.00067.2010
发表时间：
2010-09-01
影响因子：
4.9
作者：
Foster, W. Michael;Adler, Kenneth B.;Voynow, Judith A.
通讯作者：
Voynow, Judith A.
影响因子：
158.5
作者：
Corren, Jonathan;Lemanske, Robert F., Jr.;Matthews, John G.
通讯作者：
Matthews, John G.
影响因子：
168.9
作者：
Israel, E;Chinchilli, VM;Drazen, JM
通讯作者：
Drazen, JM