Chemokine release by neutrophils in chronic obstructive pulmonary disease

Abstract

Neutrophils are among the first cells to arrive at the site of injury. Chemokines secreted by neutrophils affect the migration of both neutrophils and other inflammatory cells, such as monocytes. It has been reported that LPS-induced release of IL-8 (CXCL-8) by neutrophils is amplified by neutrophil-derived TNF-α. We hypothesize that chemokine release by neutrophils is altered in chronic obstructive pulmonary disease (COPD) compared with healthy controls and that TNF-α may be involved in this alteration. Peripheral blood neutrophils isolated from smokers with COPD (n = 12), smokers without COPD (n = 12) and healthy, non-smokers (n = 12) were stimulated with LPS, TNF-α or organic dust. Anti-TNF-α Ab (infliximab) was used to study the effect of neutrophil-derived TNF-α. Release of CXCL-8, macrophage inflammatory protein-1 α (MIP-1α, CCL-3), monocyte chemotactic protein-1 (MCP-1, CCL-2) and TNF-α was measured. Neutrophils spontaneously released CXCL-8, CCL-2 and CCL-3. Inhibition of TNF-α reduced the spontaneous release of CXCL-8 and CCL-3. Stimulation with LPS and organic dust increased the release of CXCL-8 and CCL-3 (but not CCL-2) which was reduced by inhibition of TNF-α. In the COPD group, inhibition of TNF-α failed to inhibit the release of LPS-induced CXCL-8. The role of neutrophils as cytokine and chemokine producers was confirmed. Neutrophil-derived TNF-α contributed to the release of chemokines after stimulation with LPS and organic dust, as the response was inhibited by infliximab. In the COPD group, infliximab did not significantly inhibit the release of CXCL-8, suggesting that the role of TNF-α is altered in COPD.

Carbocisteine attenuates TNF-α-induced inflammation in human alveolar epithelial cells in vitro through suppressing NF-κB and ERK1/2 MAPK signaling pathways

“…MIP-1β contributes substantially to the development of lung inflammation following exposure to tobacco smoke [26] . The levels of IL-6, IL-8, TNF-α, IP-10, MCP-1, MIP-1α and MIP-1β were increased in the sputum and/or serum of patients with stable COPD or during exacerbation compared with controls [23][24][25] . Therefore, these cytokines are cardinal markers of airway inflammation in COPD patients.…”

“…IL-6 contributes to the pathogenesis of the autoimmune response observed in the lungs of the patients with more severe COPD; IL-8 plays a major role in neutrophil chemotaxis caused by alveolar macrophage-derived conditioned media of COPD; TNF-α is an important chemotactic protein for neutrophils [22] ; IP-10 is a chemokine strongly associated with viral infection of COPD [23] ; MCP-1 is involved in the migration of macrophages into the small airways, thus contributing to the inflammatory load associated with COPD [24] ; neutrophilderived MCP-1, MIP-1α, and MIP-1β are involved in macrophage recruitment into inflamed tissue during COPD [25] . MIP-1β contributes substantially to the development of lung inflammation following exposure to tobacco smoke [26] .…”

Carbocisteine attenuates hydrogen peroxide-induced inflammatory injury in A549 cells via NF-κB and ERK1/2 MAPK pathways

“…We also found that carbocisteine reduced the production of IL-6 and IL-8, decreased the expression of inflammatory cytokines such as IL-6 and TNF-α, reduced the chemokines such as IL-8, IP-10 and MIP-1β (important factors related to the pathogenesis of COPD [20][21][22][23][24]), and exhibited exceptional anti-inflammatory ability. These findings extended our study on the cytoprotective role of carbocisteine from H 2 O 2 , namely, the inhibitory effects of carbocisteine on the induction of pro-inflammatory cytokines and chemokines by H 2 O 2 .…”

Neutrophils and emerging targets for treatment in chronic obstructive pulmonary disease

“…Furthermore, components have been identified that increase the longevity of neutrophils in COPD, which substantially adds to the accumulation of these cells in the lungs. Finally, in comparison with those of healthy individuals, the neutrophils of COPD seem to respond differently to many chemical signals that normally regulate the immune response [69][70][71]. This has impeded the progress of research to the causes and especially to possible interventions for COPD.…”

“…Because of these findings, it has been suggested that TNF-a levels are the reason why the progression of COPD slows down if people quit smoking [78]. However, a later study using an TNF-a antagonist suggests the role of TNF-a is altered in COPD [71].…”