Introduction: Exposure to biomass smoke (BMS) particles in developing countries is a major cause COPD. BMS particles are phagocytosed by lung macrophages which elicit an inflammatory response. It is not yet understood which pathways are involved in this process.
Methods: BMS particles were collected from an Indian cookstove burning wood and animal dung. Monocyte-derived macrophages (MDM) were isolated from non-smokers and COPD subjects and differentiated for 12 days in GM-CSF (G-?) or M-CSF (M-?) prior exposure to 30?g/ml BMS +/- Polymixin (10?g/ml). MDM were lysed and western blots for phosphorylated and total IKB-?, P-38 and ERK were performed.
Results: Exposure of both G-? and M-? to BMS increased phosphorylation of IKB-?, P-38 and ERK at 30 and 60 min. M-? from both NS and COPD subjects were more responsive to BMS compared to G-? (Table 1). In all cases, phosphorylation could be suppressed by ~50% by inclusion of the LPS chelator, polymyxin B.
| Non- Smoker | Non-Smoker | COPD | COPD | |
| G-? | M-? | G-? | M-? | |
| IKB-? | 0.9 +/- 0.6 | 3.7 +/- 1.6 | 0.6 +/- 0.1 | 5.1 +/- 1.4* |
| P-38 | 0.3 +/- 0.1 | 0.8 +/- 0.2* | 0.7 +/- 0.1 | 0.8 +/- 0.1 |
| ERK | 0.3 +/- 0.2 | 1.3 +/- 0.4* | 0.4 +/- 0.1 | 1.4 +/- 0.2** |
Table.1: Densitometry of Phosphorylated/Total protein following 60min exposure of MDM to BMS. *p=0.05, **p=0.01 for differences between G-? and M-?
Conclusion: BMS activates macrophage IKB-?, P-38 and ERK pathways that may lead to increased inflammatory responses of these cells. Half the signal can be attributed to LPS contamination, however the particles still drive an LPS independent response. These data suggest that IKB? and MAP kinase inhibitors may reduce macrophage responses to BMS particles and potentially progression of COPD.