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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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β-Carotene and quercetin enhance the phagocytosis-inducing activity of CSE. The capacity of hMDMs to phagocytose freshly isolated neutrophils as well as neutrophils exposed to CSE (37 °C, 30 min) with and without several major antioxidants; Vit C (vitamin C, ascorbic acid); Vit E (vitamin E, α-tocopherol); βC (β-all trans β-carotene); and Quer (quercetin) was determined, as described elsewhere. Data presented are mean (±S.D.). *P<0.05; **P<0.01 between indicated means
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fig8: β-Carotene and quercetin enhance the phagocytosis-inducing activity of CSE. The capacity of hMDMs to phagocytose freshly isolated neutrophils as well as neutrophils exposed to CSE (37 °C, 30 min) with and without several major antioxidants; Vit C (vitamin C, ascorbic acid); Vit E (vitamin E, α-tocopherol); βC (β-all trans β-carotene); and Quer (quercetin) was determined, as described elsewhere. Data presented are mean (±S.D.). *P<0.05; **P<0.01 between indicated means

Mentions: As shown in Figure 7, the addition of lipid antioxidants (β-carotene or quercetin) to CSE, but not soluble antioxidants (vitamin C and vitamin E), significantly potentiated the proportion of annexin V+/ propidium iodide (PI)+ neutrophils. Similarly, β-carotene or quercetin treatment significantly increased the phagocytosis of CSE-exposed neutrophils by hMDMs (Figure 8).


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)

β-Carotene and quercetin enhance the phagocytosis-inducing activity of CSE. The capacity of hMDMs to phagocytose freshly isolated neutrophils as well as neutrophils exposed to CSE (37 °C, 30 min) with and without several major antioxidants; Vit C (vitamin C, ascorbic acid); Vit E (vitamin E, α-tocopherol); βC (β-all trans β-carotene); and Quer (quercetin) was determined, as described elsewhere. Data presented are mean (±S.D.). *P<0.05; **P<0.01 between indicated means
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig8: β-Carotene and quercetin enhance the phagocytosis-inducing activity of CSE. The capacity of hMDMs to phagocytose freshly isolated neutrophils as well as neutrophils exposed to CSE (37 °C, 30 min) with and without several major antioxidants; Vit C (vitamin C, ascorbic acid); Vit E (vitamin E, α-tocopherol); βC (β-all trans β-carotene); and Quer (quercetin) was determined, as described elsewhere. Data presented are mean (±S.D.). *P<0.05; **P<0.01 between indicated means
Mentions: As shown in Figure 7, the addition of lipid antioxidants (β-carotene or quercetin) to CSE, but not soluble antioxidants (vitamin C and vitamin E), significantly potentiated the proportion of annexin V+/ propidium iodide (PI)+ neutrophils. Similarly, β-carotene or quercetin treatment significantly increased the phagocytosis of CSE-exposed neutrophils by hMDMs (Figure 8).

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