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.
Savedra
R
R
The Maxwell Finland Laboratory for Infectious Diseases, Department of Medicine, Boston City Hospital, MA 02118, USA.
Delude
R L
RL
Ingalls
R R
RR
Fenton
M J
MJ
Golenbock
D T
DT
D000818:Animals; D001254:Astrocytoma; D016466:CHO Cells; D006224:Cricetinae; D004731:Endotoxins / Q000378:metabolism*; D005354:Fibrosarcoma; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D018950:Lipopolysaccharide Receptors / Q000502:physiology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000494:pharmacology; D009161:Mycobacterium / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D014407:Tumor Cells, Cultured
D004731:Endotoxins; D007375:Interleukin-1; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011971:Receptors, Immunologic; C048071:endotoxin receptor; C050016:lipoarabinomannan