Toll-like receptor 4 is the signal receptor for LPS, and therefore lung tissue become more susceptible to an exacerbated inflammatory response mediated by LPS through the TNF-�� pathway [18�C20].Several than conditions in feedlots could favour the maintenance of factors that contribute to or sustain the inflammatory response in the lung such as feedlot dust. Feedlot dust contains sufficient amounts of LPS to induce lung lesions and a systemic response in sheep [34, 35]. The presence of proinflammatory stimuli, such as exposure to airborne LPS, is the most likely influence that impedes healing in pneumonic cattle in feedlots [34, 35]. Correspondingly, feedlot workers are more susceptible to severe manifestations of respiratory disease and feedlot dust induces a proinflammatory cytokine profile in human bronchial epithelial cells in vitro [38].

Continuous exposure to LPS produces inflammatory changes in the mouse lung comparable to COPD in humans [39]. Similarly, chronic tobacco exposure induces epithelial squamous metaplasia in proximal airways in rats [40]. In cattle, subacute to chronic lesions of suppurative bronchopneumonia are characterized by bronchitis, bronchiolitis, pleural and parenchymal fibroplasia, atelectasis, and emphysema [9]. These histological changes are also compatible with COPD. However, in cattle, squamous metaplasia in large airways is occasionally seen in severe cases with chronic progression (Figure 1(a)). Instead, chronic bronchitis with goblet cells hyperplasia (Figure 1(a)) as well as goblet cell metaplasia in bronchioles is more common [9, 26] (Figure 1(f)).

All of these changes are AV-951 considered examples of adaptive response to persistent insult to the airways and highly representative of COPD [9, 13�C15, 40].Chronic obstructive pulmonary disease is a respiratory syndrome of multiple etiologies that provokes dyspnoea due to obstructive lesions in the intrapulmonary airways. Chronic bronchitis, chronic bronchiolitis, bronchiolitis obliterans, bronchiectasis, and emphysema associated with neutrophil infiltration, macrophages, lymphocytes, and mast cells are always present in severe cases [13�C15]. Causes of COPD in humans are diverse and include respiratory tract infections, air pollution, and smoking [13�C15, 39, 40]. For the present discussion, we considered the infectious causes and the effects of air pollution in establishing pathological analogies with cattle. It has been proposed that COPD is the result of inflammation/restoration events occurring in an unfavourable inflammatory condition leading to incomplete healing and abnormal deposition of extracellular matrix [13�C15, 29, 30]. Bronchiolitis obliterans is a common feature in COPD [13�C16].