Back to Search
Start Over
CD14 enhances cellular responses to endotoxin without imparting ligand-specific recognition.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 1995 Sep 26; Vol. 92 (20), pp. 9288-92. - Publication Year :
- 1995
-
Abstract
- Binding of the lipid A portion of bacterial lipopolysaccharide (LPS) to leukocyte CD14 activates phagocytes and initiates the septic shock syndrome. Two lipid A analogs, lipid IVA and Rhodobacter sphaeroides lipid A (RSLA), have been described as LPS-receptor antagonists when tested with human phagocytes. In contrast, lipid IVA activated murine phagocytes, whereas RSLA was an LPS antagonist. Thus, these compounds displayed a species-specific pharmacology. To determine whether the species specificity of these LPS antagonists occurred as a result of interactions with CD14, the effects of lipid IVA and RSLA were examined by using human, mouse, and hamster cell lines transfected with murine or human CD14 cDNA expression vectors. These transfectants displayed sensitivities to lipid IVA and RSLA that reflected the sensitivities of macrophages of similar genotype (species) and were independent of the source of CD14 cDNA. For example, hamster macrophages and hamster fibroblasts transfected with either mouse or human-derived CD14 cDNA responded to lipid IVA and RSLA as LPS mimetics. Similarly, lipid IVA and RSLA acted as LPS antagonists in human phagocytes and human fibrosarcoma cells transfected with either mouse or human-derived CD14 cDNA. Therefore, the target of these LPS antagonists, which is encoded in the genomes of these cells, is distinct from CD14. Although the expression of CD14 is required for macrophage-like sensitivity to LPS, CD14 cannot discriminate between the lipid A moieties of these agents. We hypothesize that the target of the LPS antagonists is a lipid A recognition protein which functions as a signaling receptor that is triggered after interaction with CD14-bound LPS.
- Subjects :
- Animals
Antigens, CD metabolism
Binding Sites
CHO Cells
Cell Nucleus physiology
Cricetinae
Cricetulus
Endotoxins pharmacology
Humans
Immunoglobulin M biosynthesis
Lipopolysaccharide Receptors metabolism
Macrophages, Peritoneal drug effects
Mice
Receptors, Antigen, B-Cell biosynthesis
Recombinant Proteins metabolism
Rhodobacter sphaeroides
Transfection
Antigens, CD physiology
Glycolipids pharmacology
Lipid A analogs & derivatives
Lipid A pharmacology
Lipopolysaccharide Receptors physiology
Macrophages, Peritoneal immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 92
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 7568119
- Full Text :
- https://doi.org/10.1073/pnas.92.20.9288