Mycobacterial lipoarabinomannan recognition requires a receptor that shares components of the endotoxin signaling system
Phagocytic leukocytes respond to a variety of bacterial products including Gram-negative bacterial LPS and mycobacterial lipoarabinomannan (LAM). Anti-CD14 mAbs have been shown to block LPS and LAM activation of myeloid cells, suggesting that CD14 is required for cellular recognition of both ligands. Activation of undifferentiated promonomyelocytic THP-1 cells with LAM or LPS under serum-free conditions was enhanced in the presence of recombinant soluble CD14 (rsCD14). LPS binding protein (LBP), which is present in normal serum, further enhanced the sensitivity of undifferentiated THP-1 cells to both ligands even in the absence of rsCD14. Although CD14-transfected Chinese hamster ovary and human HT1080 fibrosarcoma cell lines can be activated by LPS, neither cell line was activated by LAM. Furthermore, U373 astrocytoma cells, which respond to LPS using sCD14 and LBP, failed to be activated by LAM in the presence of rsCD14 and rLBP. We then tested the effects of lipid IVA and Rhodobacter sphaeroides lipid A, compounds that function as endotoxin inhibitors in human cells by interacting with a molecule thought to be a CD14-dependent LPS signal transducer. Both lipid IVA and R. sphaeroides lipid A inhibited the effects of LPS and LAM in THP-1 cells. Thus, the LPS and LAM receptors share CD14, LBP, and a putative endotoxin antagonist-inhibitable signal transducing component. However, the LAM signaling system appears to require an additional receptor component whose expression is restricted to cells of hemopoietic origin.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
1996 |
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| Erschienen: |
1996 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:157 |
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| Enthalten in: |
Journal of immunology (Baltimore, Md. : 1950) - 157(1996), 6 vom: 15. Sept., Seite 2549-54 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Savedra, R [VerfasserIn] |
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| Anmerkungen: |
Date Completed 12.12.1996 Date Revised 16.11.2017 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM08775181X |
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| 100 | 1 | |a Savedra, R |c Jr |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Mycobacterial lipoarabinomannan recognition requires a receptor that shares components of the endotoxin signaling system |
| 264 | 1 | |c 1996 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 12.12.1996 | ||
| 500 | |a Date Revised 16.11.2017 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Phagocytic leukocytes respond to a variety of bacterial products including Gram-negative bacterial LPS and mycobacterial lipoarabinomannan (LAM). Anti-CD14 mAbs have been shown to block LPS and LAM activation of myeloid cells, suggesting that CD14 is required for cellular recognition of both ligands. Activation of undifferentiated promonomyelocytic THP-1 cells with LAM or LPS under serum-free conditions was enhanced in the presence of recombinant soluble CD14 (rsCD14). LPS binding protein (LBP), which is present in normal serum, further enhanced the sensitivity of undifferentiated THP-1 cells to both ligands even in the absence of rsCD14. Although CD14-transfected Chinese hamster ovary and human HT1080 fibrosarcoma cell lines can be activated by LPS, neither cell line was activated by LAM. Furthermore, U373 astrocytoma cells, which respond to LPS using sCD14 and LBP, failed to be activated by LAM in the presence of rsCD14 and rLBP. We then tested the effects of lipid IVA and Rhodobacter sphaeroides lipid A, compounds that function as endotoxin inhibitors in human cells by interacting with a molecule thought to be a CD14-dependent LPS signal transducer. Both lipid IVA and R. sphaeroides lipid A inhibited the effects of LPS and LAM in THP-1 cells. Thus, the LPS and LAM receptors share CD14, LBP, and a putative endotoxin antagonist-inhibitable signal transducing component. However, the LAM signaling system appears to require an additional receptor component whose expression is restricted to cells of hemopoietic origin | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, P.H.S. | |
| 650 | 7 | |a Endotoxins |2 NLM | |
| 650 | 7 | |a Interleukin-1 |2 NLM | |
| 650 | 7 | |a Lipopolysaccharide Receptors |2 NLM | |
| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a Receptors, Immunologic |2 NLM | |
| 650 | 7 | |a endotoxin receptor |2 NLM | |
| 650 | 7 | |a lipoarabinomannan |2 NLM | |
| 700 | 1 | |a Delude, R L |e verfasserin |4 aut | |
| 700 | 1 | |a Ingalls, R R |e verfasserin |4 aut | |
| 700 | 1 | |a Fenton, M J |e verfasserin |4 aut | |
| 700 | 1 | |a Golenbock, D T |e verfasserin |4 aut | |
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