Neutrophil CD14: biochemical properties and role in the secretion of tumor necrosis factor-alpha in response to lipopolysaccharide.
CD14 is a myeloid cell differentiation Ag expressed primarily by monocytes and macrophages. CD14 has recently been shown to function as a receptor for a complex of LPS and LPS binding protein (LBP), an acute phase serum protein also present in normal serum in trace amounts. In the presence of LBP, LPS strongly activates monocytes via CD14 as measured by TNF secretion. This pathway of monocyte activation is thought to be a major contributor to the symptoms of endotoxin shock. Another major cell type involved in the response to Gram-negative infection is the neutrophil. Recent studies have shown that neutrophils also express CD14 and suggest that they can respond to LPS through a similar pathway. However, the biochemical nature of neutrophil CD14 has not previously been described. In this report, we have analyzed several biochemical characteristics of neutrophil CD14. We show that CD14 is actively synthesized by neutrophils as a glycosylphosphatidyl-inositol-anchored protein, indistinguishable in size from monocyte CD14. Furthermore, neutrophils, like monocytes, shed a smaller soluble form of CD14 into culture supernatants. In addition, like monocytes, neutrophils respond to LPS/LBP complexes via CD14 by releasing TNF-alpha. The described properties and function of neutrophil CD14 suggest that it may directly participate in the acute inflammatory response and in endotoxin shock.
Haziot
A
A
Department of Medicine, North Shore University Hospital/Cornell University Medical College, Manhasset, NY 11030.
Tsuberi
B Z
BZ
Goyert
S M
SM
D000209:Acute-Phase Proteins; D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000502:physiology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis / Q000502:physiology*; D002352:Carrier Proteins / Q000494:pharmacology; D017261:Glycosylphosphatidylinositols / Q000502:physiology; D006801:Humans; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008562:Membrane Glycoproteins; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002352:Carrier Proteins; D017261:Glycosylphosphatidylinositols; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein