A mouse GM-CSF receptor antibody attenuates neutrophilia in mice exposed to cigarette smoke

被引：20

作者：

Botelho, F. M. ^{[2
]}

Nikota, J. K. ^{[3
]}

Bauer, C. ^{[3
]}

Davis, N. H. E. ^{[1
]}

Cohen, E. S. ^{[1
]}

Anderson, I. K. ^{[1
]}

Coyle, A. J. ^{[5
]}

Kolbeck, R. ^{[5
]}

Humbles, A. A. ^{[5
]}

Staempfli, M. R. ^{[2
,4
]}

Sleeman, M. A. ^{[1
]}

机构：

[1] MedImmune LLC, Dept Resp Autoimmun & Inflammat, Cambridge CB21 6GH, England

[2] McMaster Univ, Ctr Gene Therapeut, Dept Pathol & Mol Med, Hamilton, ON, Canada

[3] McMaster Univ, Med Sci Grad Program, Hamilton, ON, Canada

[4] McMaster Univ, Dept Med, Hamilton, ON, Canada

[5] MedImmune LLC, Dept Resp Autoimmun & Inflammat, Gaithersburg, MD USA

来源：

EUROPEAN RESPIRATORY JOURNAL | 2011年 / 38卷 / 02期

关键词：

Antibody neutralisation; cigarette smoke; granulocyte-macrophage colony-stimulating factor; inflammation; neutrophils; COLONY-STIMULATING FACTOR; OBSTRUCTIVE PULMONARY-DISEASE; NF-KAPPA-B; IN-VIVO; MATRIX METALLOPROTEINASE-12; AIRWAY INFLAMMATION; LUNG INFLAMMATION; INNATE IMMUNITY; COPD; EXPRESSION;

D O I：

10.1183/09031936.00076210

中图分类号：

R56 [呼吸系及胸部疾病];

学科分类号：

100201 [内科学];

摘要：

We investigated the role of granulocyte-macrophage colony-stimulating factor (GMCSF) in a subchronic exposure model of cigarette smoke (CS)-induced inflammation using antibodies directed against GM-CSF or the GM-CSF receptor (GM-CSFR) alpha-chain. CS-induced mononuclear and neutrophilic inflammation following 4 days of CS exposure in BALB/c mice was assessed in bronchoalveolar lavage (BAL) fluid. An increase in mature dendritic cells (DCs) (CD11c+ and major histocompatibility complex II+) and Gr-1-high neutrophils was also observed by flow cytometric analysis of whole-lung tissue. Daily i.p. injection of 400 mg GM-CSF or GM-CSFR antibody prior to daily smoke exposure attenuated the accumulation of neutrophils within the BAL by 60%. A reduction in mature DCs was also observed. Anti-GM-CSFR antibody administration did not have an effect on the percentage of lung T-cells; however, a significant decrease in activated CD69+ CD8+ T-cells was observed. Anti-GM-CSFR antibody administration decreased the mRNA and protein expression of interleukin-12 p40 and matrix metalloproteinase 12. Taken together, intervention with this receptor antibody implicates the GM-CSF pathway as an important mediator of smoke-induced inflammation.

引用

页码：285 / 294

页数：10

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