Neutralizing Granulocyte/Macrophage Colony–Stimulating Factor Inhibits Cigarette Smoke–induced Lung Inflammation

• DOI: 10.1164/rccm.200912-1794oc
• Publication Date: 2010-03-05T03:42:55Z
• Authors: Ross Vlahos; Steven Bozinovski; Sheau Pyng Jamie ...; Stefan Ivanov; Anders Lindén; John A. Hamilton; Gary P. Anderson
• Keywords: Male; Mice; Mice, Inbred BALB C; 0303 health sciences; 03 medical and health sciences; Smoking; Animals; Granulocyte-Macrophage Colony-Stimulating Factor; Pneumonia; Antibodies, Neutralizing; Immunity, Innate; 3. Good health

Cigarette smoke is the major cause of chronic obstructive pulmonary disease (COPD), and there currently no satisfactory therapy to treat people with COPD. We have previously shown that granulocyte/macrophage colony-stimulating factor (GM-CSF) regulates lung innate immunity LPS through Akt/Erk activation nuclear factor-kappaB activator protein (AP)-1.The aim this study was determine whether neutralization GM-CSF can inhibit cigarette smoke-induced inflammation in vivo.Male BALB/c mice were exposed generated from 9 cigarettes per day for 4 days. Mice treated intranasally 100 microg 22E9 (anti-GM-CSF mAb) isotype control antibody on Days 2 4, 1 hour before or sham exposure. On fifth killed, lungs lavaged PBS then harvested genomic proteomic analysis.Cigarette smoke-exposed anti-GM-CSF mAb had significantly less BALF macrophages neutrophils, whole TNF-alpha, macrophage inflammatory (MIP)-2, matrix metalloproteinase (MMP)-12 mRNA expression lost weight compared control. In contrast, increases MMP-9 net gelatinase activity unaffected by treatment anti-GM-CSF. addition, did not affect phagocytic function alveolar macrophages.GM-CSF a key mediator airways inflammation, its may therapeutic implications diseases such as