Human CD14 mediates recognition and phagocytosis of apoptotic cells.
Cells undergoing programmed cell death (apoptosis) are cleared rapidly in vivo by phagocytes without inducing inflammation. Here we show that the glycosylphosphatidylinositol-linked plasma-membrane glycoprotein CD14 on the surface of human macrophages is important for the recognition and clearance of apoptotic cells. CD14 can also act as a receptor that binds bacterial lipopolysaccharide (LPS), triggering inflammatory responses. Overstimulation of CD14 by LPS can cause the often fatal toxic-shock syndrome. Here we show that apoptotic cells interact with CD14, triggering phagocytosis of the apoptotic cells. This interaction depends on a region of CD14 that is identical to, or at least closely associated with, a region known to bind LPS. However, apoptotic cells, unlike LPS, do not provoke the release of pro-inflammatory cytokines from macrophages. These results indicate that clearance of apoptotic cells is mediated by a receptor whose interactions with 'non-self' components (LPS) and 'self' components (apoptotic cells) produce distinct macrophage responses.
Devitt
A
A
Department of Immunology, University of Birmingham Medical School, UK.
Moffatt
O D
OD
Raykundalia
C
C
Capra
J D
JD
Simmons
D L
DL
Gregory
C D
CD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis / Q000502:physiology*; D001665:Binding Sites; D019556:COS Cells; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018922:HL-60 Cells; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000502:physiology; D010587:Phagocytosis / Q000502:physiology*; D017634:Self Tolerance; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018985:Epitopes, B-Lymphocyte; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha