Intranasal organic dust exposure-induced airway adaptation response marked by persistent lung inflammation and pathology in mice

American Journal of Physiology - Lung Cellular and Molecular Physiology - Tập 296 Số 6 - Trang L1085-L1095 - 2009
Jill Poole1, Todd A. Wyatt2, Peter J. Oldenburg3, Margaret K. Elliott4, William W. West4, Joseph H. Sisson5, Susanna G. Von Essen5, Debra J. Romberger5
1Central States Center for Agricultural Safety & Health
2Environmental, Agricultural & Occupational Health Sciences
3Pharmacology & Experimental Neuroscience (PEN)
4University of Nebraska Medical Center
5Pulmonary, Critical Care, & Sleep Medicine

Tóm tắt

Organic dust exposure in agricultural environments results in an inflammatory response that attenuates over time, but repetitive exposures can result in chronic respiratory disease. Animal models to study these mechanisms are limited. This study investigated the effects of single vs. repetitive dust-induced airway inflammation in mice by intranasal exposure method. Mice were exposed to swine facility dust extract (DE) or saline once and once daily for 1 and 2 wk. Dust exposure resulted in increased bronchoalveolar lavage fluid neutrophils and macrophages after single and repetitive exposures. Lavage fluid TNFα, IL-6, keratinocyte chemoattractant, and macrophage inflammatory protein-2 were significantly increased after single and repetitive dust exposures, but were dampened in 2-wk dust-exposed mice compared with single exposure. Dust exposure induced PKCα and -ε activation in isolated tracheal epithelial cells but were dampened with repetitive exposures. Ex vivo stimulation of alveolar macrophages from 2-wk animals demonstrated reduced cytokine responsiveness and phagocytic ability. Significant lung pathology occurred with development of mixed mononuclear cellular aggregates (T and B lymphocytes, phagocytes) after repetitive dust exposure, a novel observation. Airway hyperresponsiveness to methacholine occurred after single dust exposure but resolved after 2 wk. Collectively, intranasal exposure to DE results in significant lung inflammatory and pathological responses marked by a modulated innate immune response to single and repetitive dust exposures that is associated with PKC activity.

Từ khóa


Tài liệu tham khảo

10.1016/j.jaci.2006.02.030

10.1056/NEJMp048102

10.1186/1465-9921-9-7

10.1067/mai.2003.108

10.1016/j.jaci.2007.03.051

10.1289/ehp.866637

10.1016/j.lfs.2007.01.048

10.1186/1465-9921-6-50

10.1080/01902140701807779

10.1016/j.jaci.2008.01.010

10.1164/ajrccm.155.1.9001321

10.1172/JCI117556

10.1080/01902140600710546

10.1165/rcmb.2005-0440OC

10.4049/jimmunol.180.5.3478

10.1023/A:1021464718376

10.1038/nm1246

10.1165/rcmb.2004-0309OC

10.1002/ajim.4700250115

10.1164/ajrccm.150.4.7921472

Lefort J, Singer M, Leduc D, Renesto P, Nahori MA, Huerre M, Creminon C, Chignard M, Vargaftig BB.Systemic administration of endotoxin induces bronchopulmonary hyperreactivity dissociated from TNF-alpha formation and neutrophil sequestration into the murine lungs.J Immunol161: 474–480, 1998.

10.1016/j.molimm.2007.05.030

10.1152/japplphysiol.00384.2003

10.1016/j.envres.2008.05.004

10.1080/01902140290096728

10.4049/jimmunol.181.5.3698

10.1152/ajplung.00487.2007

10.5271/sjweh.673

10.1183/09031936.98.12010045

10.1016/j.jaci.2008.05.023

10.1016/j.jaci.2007.04.033

10.1152/japplphysiol.00815.2001

10.1152/ajplung.00420.2001

10.1164/ajrccm.151.1.7812571

10.1080/08958370701866412

10.1164/rccm.200410-1384SO

10.13031/2013.13684

10.1002/ajim.4700250122

10.1164/ajrccm/138.4.921

10.1165/rcmb.2003-0062OC

10.1183/09031936.97.10020381

10.1080/01926230600941340

West MA, Heagy W.Endotoxin tolerance: a review.Crit Care Med30: S64–S73, 2002.

10.1016/S0002-9440(10)63475-X

10.1183/09031936.00015007

10.1152/ajplung.00103.2007

10.1152/ajplung.1998.275.4.L827

Thông tin
Thông tin xuất bản

American Journal of Physiology - Lung Cellular and Molecular Physiology

Tập 296 Số 6

L1085-L1095

Thông tin tác giả