Cigarette smoke inhibits macrophage sensing of Gram‐negative bacteria and lipopolysaccharide: relative roles of nicotine and oxidant stress

Abstract

Background and purpose: Smoking cigarettes is a major risk factor for the development of cardiovascular and respiratory disease. Moreover, smokers are more prone to infections. This has been associated with a suppression of the immune system by smoke. However, it is not clear how cigarette smoke affects the ability of immune cells to sense pathogens. Cigarette smoke contains a large number of molecules which may mediate responses on immune cells and of these, nicotine and oxidants have both been identified as inhibitory for the sensing of bacterial lipopolysaccharide (LPS). Nitric oxide synthase (NOS) and tumour necrosis factor (TNF)-a are both induced in macrophages on stimulation with Gram negative bacteria or LPS. Experimental approach: We used murine macrophages stimulated with whole heat-killed bacteria or LPS. We measured output of NO (as nitrite) and TNFa, NOS protein by Western blotting and cellular oxidant stress. Key results: Cigarette smoke extract suppressed the ability of murine macrophages to release NO, but not TNFa in response to whole bacteria. Cigarette smoke extract also inhibited nitric oxide synthase II protein expression in response to LPS. The effects of cigarette smoke extract on nitrite formation stimulated by LPS were unaffected by inhibition of nicotinic receptors with a-bungarotoxin (100 units ml À1 ). However, the effects of cigarette smoke extract on LPS-induced nitrite formation were mimicked by hydrogen peroxide and reversed by the anti-oxidants N-acetyl cysteine and glutathione. Conclusions and implications: We suggest that cigarette smoke exerts its immunosuppressive effects through an oxidantdependent and not a nicotine-dependent mechanism.

Cigarette Smoke Inhibits Airway Epithelial Cell Innate Immune Responses to Bacteria

“…CS contains a high concentration of free radicals and other oxidants, such as nitric oxide (NO), superoxide anions, hydroxyl radical, and hydrogen peroxide, which cause direct and indirect damage to a variety of cell types (4,14,19,24,31,32). Treatment of CSC with 25 mM antioxidant NAC abrogated the inhibitory effect of CSC on NT H. influenzae-induced IL-8 production.…”

Sepsis in head and neck cancer patients treated with chemotherapy and radiation: Literature review and consensus

“…The panel adopted the nomenclature and definitions for terms used by 2001 International Sepsis Definitions [46,47] and alcohol [48] consumption, malnutrition [82,157], swallowing impairment with aspiration [45], chemotherapy-induced neutropenia [39,158,159], disruption of physiological barriers as a consequence of radiodermitis and mucositis [40,160], gingival pockets and dental caries [161][162][163][164], age [12,165,166], co-morbidities such as diabetes and chronic obstructive pulmonary disease (COPD) [166], and the presence of central venous catheters, gastrostomy and tracheostomy are at a higher risk of infections. Conference (i.e.…”

“…The main infection sources in HNCPs are the respiratory tract, the oral cavity, and medical devices such as central venous catheters (CVCs) [122], especially total implanted access ports [123], gastrostomy [124], and tracheostomy [47].…”

Cigarette Smoke Increases Staphylococcus aureus Biofilm Formation via Oxidative Stress

“…The high concentrations of a variety of free radicals and reactive oxygen species, such as nitrous oxide (NO Ϫ ), superoxide anions, hydroxyl radicals, and hydrogen peroxide, present in the CS alters important signaling pathways, leading to immunomodulatory effects (6,35,44,45,64,67 (16). Pretreatment of CS with an antioxidant compound (NAC) significantly abrogated induction of staphylococcal biofilm formation.…”