Macrophage phagocytosis of apoptotic neutrophils is compromised by matrix proteins modified by cigarette smoke and lipid peroxidation products.
Clearance of apoptotic cells by phagocytosis plays an important role in the resolution of an inflammatory response. Macrophages interacting with extracellular matrix (ECM) proteins upregulate their phagocytic capacity. Cigarette smoke contains highly reactive carbonyls that modify proteins which directly/indirectly affects cellular function. We observed, in vitro, that human macrophages interacting with carbonyl or cigarette smoke modified ECM proteins dramatically down regulated their ability to phagocytose apoptotic neutrophils. We also show that this interaction with carbonyl-adduct modified ECM proteins led to increased macrophage adhesion in vitro. We hypothesise that changes in the ECM environment as a result of cigarette smoking affect the ability of macrophages to remove apoptotic cells. Moreover, we postulate that this decreased phagocytic activity was as a result of sequestration of receptors involved in the uptake of apoptotic cells towards that of recognition of carbonyl adducts on the modified ECM proteins leading to increased macrophage adhesion.
Kirkham
Paul A
PA
Novartis Institute for Biomedical Research (Horsham), West Sussex, UK. paul.kirkham@pharma.novartis.com
Spooner
Gillian
G
Rahman
Irfan
I
Rossi
Adriano G
AG
D000447:Aldehydes / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D024141:Collagen Type IV / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology; D006801:Humans; D018960:Hyaluronan Receptors / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism; D010587:Phagocytosis; D012907:Smoking / Q000009:adverse effects* / Q000473:pathology; D020298:U937 Cells
D000447:Aldehydes; D024141:Collagen Type IV; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D018960:Hyaluronan Receptors; C027576:4-hydroxy-2-nonenal