A new insight into phagocytosis of apoptotic cells: proteolytic enzymes divert the recognition and clearance of polymorphonuclear leukocytes by macrophages.
The recognition of phosphatidylserine (PS) on the surface of any apoptotic cell is considered to be a key event for its clearance. We challenge this concept by showing that pretreatment of neutrophils with either host or bacterial protease affects their uptake by human monocyte-derived macrophages without having an effect on cell-surface PS presentation. Specifically, whereas preincubation of apoptotic neutrophils with cathepsin G or thrombin significantly inhibited their uptake, gingipains R or clostripain enhanced phagocytosis by macrophages. Moreover, bacterial proteinases sensitized healthy neutrophils for uptake by macrophages, whereas endogenous proteinases were unable to elicit this effect. This stimulation was apparently owing to the combined effect of proteolytic cleavage of an antiphagocytic signal (CD31) and the generation of a novel 'eat-me' signal on the neutrophil surface. These results argue that neutrophil recognition and phagocytosis by macrophages is mediated by a protein ligand whose proteolytic modification could affect the local inflammatory process.
Guzik
K
K
Department of Immunology, Faculty of Biotechnology, Jagiellonian University, Krakow, Poland.
Bzowska
M
M
Smagur
J
J
Krupa
O
O
Sieprawska
M
M
Travis
J
J
Potempa
J
J
D018829:Adhesins, Bacterial / Q000378:metabolism; D017209:Apoptosis; D003546:Cysteine Endopeptidases / Q000378:metabolism; D000080867:Gingipain Cysteine Endopeptidases; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D008264:Macrophages / Q000502:physiology*; D009504:Neutrophils / Q000166:cytology*; D010447:Peptide Hydrolases / Q000378:metabolism*; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism
D018829:Adhesins, Bacterial; D000080867:Gingipain Cysteine Endopeptidases; D008081:Liposomes; D010718:Phosphatidylserines; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; C019913:clostripain