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Cigarette smoke-exposed neutrophils die unconventionally but are rapidly phagocytosed by macrophages.

Guzik K, Skret J, Smagur J, Bzowska M, Gajkowska B, Scott DA, Potempa JS - Cell Death Dis (2011)

Bottom Line: Accumulation of tar-like substances in autophagosomes is also apparent.Blockade of LOX-1 and scavenger receptor A, but not MARCO or CD36, as well as pre-incubation with oxLDL, inhibited phagocytosis, suggesting that oxLDL-like structures are major phagocytosis signals.Specific lipid (β-carotene and quercetin), but not aqueous, antioxidants increased the pro-phagocytic effects of CSE.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.

ABSTRACT
Pulmonary accumulation of neutrophils is typical for active smokers who are also predisposed to multiple inflammatory and infectious lung diseases. We show that human neutrophil exposure to cigarette smoke extract (CSE) leads to an atypical cell death sharing features of apoptosis, autophagy and necrosis. Accumulation of tar-like substances in autophagosomes is also apparent. Before detection of established cell death markers, CSE-treated neutrophils are effectively recognized and non-phlogistically phagocytosed by monocyte-derived macrophages. Blockade of LOX-1 and scavenger receptor A, but not MARCO or CD36, as well as pre-incubation with oxLDL, inhibited phagocytosis, suggesting that oxLDL-like structures are major phagocytosis signals. Specific lipid (β-carotene and quercetin), but not aqueous, antioxidants increased the pro-phagocytic effects of CSE. In contrast to non-phlogistic phagocytosis, degranulation of secondary granules, as monitored by lactoferrin release, was apparent on CSE exposure, which is likely to promote pulmonary inflammation and tissue degradation. Furthermore, CSE-exposed neutrophils exhibited a compromised ability to ingest the respiratory pathogen, Staphylococcus aureus, which likely contributes to bacterial persistence in the lungs of smokers and is likely to promote further pulmonary recruitment of neutrophils. These data provide mechanistic insight into the lack of accumulation of apoptotic neutrophil populations in the lungs of smokers and their increased susceptibility to degradative pulmonary diseases and bacterial infections.

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CSE-treated neutrophils lose their ability to effectively phagocytose S. aureus. Phagocytosis of opsonized, FITC-labeled ATCC 25923 (a) and Newmann (b) S. aureus strains was assessed by flow cytometry. Representative traces of bacteria engulfed by control neutrophils and CSE-treated neutrophils are demarcated by thin and thick lines, respectively. Autofluorescence signals are demarcated by the gray areas (untreated neutrophils) and dotted lines (CSE-treated cells) and correspond to neutrophils without ingested bacteria. Inset graphs represent the mean (±S.D.) percentage of bacteria-containing neutrophils with the white and gray bars representing control and CSE-exposed neutrophils, respectively. ***P<0.001, compared with unexposed, control neutrophils
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fig9: CSE-treated neutrophils lose their ability to effectively phagocytose S. aureus. Phagocytosis of opsonized, FITC-labeled ATCC 25923 (a) and Newmann (b) S. aureus strains was assessed by flow cytometry. Representative traces of bacteria engulfed by control neutrophils and CSE-treated neutrophils are demarcated by thin and thick lines, respectively. Autofluorescence signals are demarcated by the gray areas (untreated neutrophils) and dotted lines (CSE-treated cells) and correspond to neutrophils without ingested bacteria. Inset graphs represent the mean (±S.D.) percentage of bacteria-containing neutrophils with the white and gray bars representing control and CSE-exposed neutrophils, respectively. ***P<0.001, compared with unexposed, control neutrophils

Mentions: The ability of respiratory tract neutrophils to effectively phagocytose, and subsequently destroy, bacterial pathogens is critical in the prevention of pulmonary infectious diseases. As is clearly shown in Figure 9, CSE-treatment of neutrophils rendered these granulocytes ineffective in ingesting two different strains of S. aureus. Indeed, the suppression of phagocytotic capacity was dramatic, with <15% of CSE-exposed neutrophils containing fluorescein isothiocyanate (FITC)-labeled bacteria, compared with over 60% of control, unexposed neutrophils.


Cigarette smoke-exposed neutrophils die unconventionally but are rapidly phagocytosed by macrophages.

Guzik K, Skret J, Smagur J, Bzowska M, Gajkowska B, Scott DA, Potempa JS - Cell Death Dis (2011)

CSE-treated neutrophils lose their ability to effectively phagocytose S. aureus. Phagocytosis of opsonized, FITC-labeled ATCC 25923 (a) and Newmann (b) S. aureus strains was assessed by flow cytometry. Representative traces of bacteria engulfed by control neutrophils and CSE-treated neutrophils are demarcated by thin and thick lines, respectively. Autofluorescence signals are demarcated by the gray areas (untreated neutrophils) and dotted lines (CSE-treated cells) and correspond to neutrophils without ingested bacteria. Inset graphs represent the mean (±S.D.) percentage of bacteria-containing neutrophils with the white and gray bars representing control and CSE-exposed neutrophils, respectively. ***P<0.001, compared with unexposed, control neutrophils
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3101810&req=5

fig9: CSE-treated neutrophils lose their ability to effectively phagocytose S. aureus. Phagocytosis of opsonized, FITC-labeled ATCC 25923 (a) and Newmann (b) S. aureus strains was assessed by flow cytometry. Representative traces of bacteria engulfed by control neutrophils and CSE-treated neutrophils are demarcated by thin and thick lines, respectively. Autofluorescence signals are demarcated by the gray areas (untreated neutrophils) and dotted lines (CSE-treated cells) and correspond to neutrophils without ingested bacteria. Inset graphs represent the mean (±S.D.) percentage of bacteria-containing neutrophils with the white and gray bars representing control and CSE-exposed neutrophils, respectively. ***P<0.001, compared with unexposed, control neutrophils
Mentions: The ability of respiratory tract neutrophils to effectively phagocytose, and subsequently destroy, bacterial pathogens is critical in the prevention of pulmonary infectious diseases. As is clearly shown in Figure 9, CSE-treatment of neutrophils rendered these granulocytes ineffective in ingesting two different strains of S. aureus. Indeed, the suppression of phagocytotic capacity was dramatic, with <15% of CSE-exposed neutrophils containing fluorescein isothiocyanate (FITC)-labeled bacteria, compared with over 60% of control, unexposed neutrophils.

Bottom Line: Accumulation of tar-like substances in autophagosomes is also apparent.Blockade of LOX-1 and scavenger receptor A, but not MARCO or CD36, as well as pre-incubation with oxLDL, inhibited phagocytosis, suggesting that oxLDL-like structures are major phagocytosis signals.Specific lipid (β-carotene and quercetin), but not aqueous, antioxidants increased the pro-phagocytic effects of CSE.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.

ABSTRACT
Pulmonary accumulation of neutrophils is typical for active smokers who are also predisposed to multiple inflammatory and infectious lung diseases. We show that human neutrophil exposure to cigarette smoke extract (CSE) leads to an atypical cell death sharing features of apoptosis, autophagy and necrosis. Accumulation of tar-like substances in autophagosomes is also apparent. Before detection of established cell death markers, CSE-treated neutrophils are effectively recognized and non-phlogistically phagocytosed by monocyte-derived macrophages. Blockade of LOX-1 and scavenger receptor A, but not MARCO or CD36, as well as pre-incubation with oxLDL, inhibited phagocytosis, suggesting that oxLDL-like structures are major phagocytosis signals. Specific lipid (β-carotene and quercetin), but not aqueous, antioxidants increased the pro-phagocytic effects of CSE. In contrast to non-phlogistic phagocytosis, degranulation of secondary granules, as monitored by lactoferrin release, was apparent on CSE exposure, which is likely to promote pulmonary inflammation and tissue degradation. Furthermore, CSE-exposed neutrophils exhibited a compromised ability to ingest the respiratory pathogen, Staphylococcus aureus, which likely contributes to bacterial persistence in the lungs of smokers and is likely to promote further pulmonary recruitment of neutrophils. These data provide mechanistic insight into the lack of accumulation of apoptotic neutrophil populations in the lungs of smokers and their increased susceptibility to degradative pulmonary diseases and bacterial infections.

Show MeSH
Related in: MedlinePlus