Monocyte antigen CD14 is a phospholipid anchored membrane protein

Simmons, DL; Tan, Shencao; Tenen, DG; Nicholson‐Weller, Anne; Seed, Brian

doi:10.1182/blood.v73.1.284.bloodjournal731284

Cited by 56 publications

(68 citation statements)

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“…For this purpose, the following primers were used: 5Ј primer, G GGA TCC ATG GAG CGC GCG TCC TGC TTG T; 3Ј primer, G GAA TTC GTC TTG GAT CTT AGG CAA AGC. The sequence of the CD14 cDNA was identical to the published sequence except for a base substitution at position 803 (A changed to G), also reported by others (64).…”

Section: Methodssupporting

confidence: 73%

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Endotoxin activates human vascular smooth muscle cells despite lack of expression of CD14 mRNA or endogenous membrane CD14

et al. 1995

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During infection or inflammation, cells of the blood vessel wall, such as endothelial cells (EC) and smooth muscle cells (SMC), contribute to the regulation of the immune response by production of cytokines or expression of adhesion molecules. Little is known about the mechanism(s) involved in the stimulation of vascular cells by endotoxin (lipopolysaccharide [LPS]). As reported previously, LPS antagonists reduce LPS-induced cytokine production or adhesion in vitro specifically, suggesting a specific LPS recognition mechanism. We thus investigated the role of CD14 for stimulation of vascular SMC by LPS. Complement-fixing antibodies directed against CD14 (LeuM3, RoMo I, or Mo2) lysed monocytes but failed to mediate lysis of EC or SMC, indicating the lack of endogenous membrane CD14 in vascular cells. In addition, we did not detect expression of CD14 protein on EC and SMC in cell sorting analysis or cell immunoassay experiments. These observations are in line with our finding that a CD14 probe did not hybridize with mRNA of EC or SMC in Northern (RNA) blot experiments, although it hybridized well with monocyte-derived mRNA. We obtained the same results with the much more sensitive reverse transcription-PCR. Since the vascular SMC did not express endogenous CD14, we investigated the role of human serum-derived soluble CD14 (sCD14) for activation of SMC by LPS. In medium containing human serum, anti-CD14 antibodies inhibited activation of SMC by LPS. In contrast, the same antibodies did not inhibit activation of cells cultured in medium containing fetal calf serum. SMC cultured in sCD14-depleted medium responded 1,000-fold less to LPS than cells cultured in presence of sCD14. Reconstitution of sCD14-depleted serum or supplementation of serum-free medium with recombinant CD14 restored the capacity of the cells to respond to LPS. These results show that specific activation of vascular SMC by LPS does not involve binding to endogenous membrane CD14, but that the activation of vascular SMC by LPS is mediated to a great extent by serum-derived sCD14.

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Section: Methodssupporting

confidence: 73%

“…One protein unequivocally identified as an LPS receptor is the CD14 molecule (18). This cell surface molecule is anchored in the membrane by phosphatidylinositol linkage (21,64). An additional substance, the LPS-binding protein (LBP) (60,70), enhances the response of macrophages to endotoxin (47).…”

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confidence: 99%

Endotoxin activates human vascular smooth muscle cells despite lack of expression of CD14 mRNA or endogenous membrane CD14

et al. 1995

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“…CD14 as a 53-kD phosphatidylinositol-linked membrane glycoprotein is a marker of human monocytes and serves a receptor for endotoxin [1,2]. A soluble form of CD14 (48-kD sCD14) has been demonstrated in supernatants of cultured CD14 cells [3] as well as in serum and urine [4,5].…”

Section: Introductionmentioning

confidence: 99%

Elevated levels of soluble CD14 in serum of patients with acute Plasmodium falciparum malaria

Wenisch

Parschalk

et al. 1996

Clinical and Experimental Immunology

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Serum sCD14, tumour necrosis factor‐alpha (TNF‐α), IL‐6, and endotoxin were analysed in 45 patients with complicated malaria, in 14 patients with Gram‐negative septicaemia and in 24 healthy subjects by ELISA. Malaria patients with renal failure (n=16) had higher levels than patients without renal failure (n=29) (8116+1440 μg/lversus 9453+1017 μg/lP<0.05) and both had higher levels than patients with septicaemia (6155+1635μg/l) and normal subjects (2776+747 μg/l). A significant correlation between sCD14 and IL‐6 (r=0.756) and TNF (r=0.822) existed. However, no relation between sCD14 and serum endotoxin or indices of clinical disease severity (parasitaemia, fever, parasite or fever clearance time) was seen. Although the role of sCD14 in malaria remains to be determined, elevated levels may participate in the inflammatory response in complicated malaria.

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“…The 53-kD membrane antigen CD14 is a glycosyl-phosphatidylinositol (GPI)-anchored cell surface molecule expressed primarily on peripheral blood monocytes and macrophages [1,2]. Granulocytes and neutrophils also show a weak CD14 expression which can be stimulated by several factors [3.4].…”

Section: Introductionmentioning

confidence: 99%

Increased soluble CD14 serum levels and altered CD14 expression of peripheral blood monocytes in HIV-infected patients

Nockher¹,

Bergmann

Scherberich³

1994

Clinical and Experimental Immunology

133

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SUMMARYSerum levels of soluble CD14 were elevated in HIV-infected asymptomatic patients or those with lymphadetiopathy (CDC II/III) 2-9±0-8mg//compared with normal controls with 22±0-47 mgjiP < 0001. A further rise was seen in patietits with ARC (CDC rVA) 3-8 ill mg//,/' < 0 01 and patients with AIDS (CDC IVB D) 5 7±2-5mg//. P < 0 01. Although absolute nutnbers of CDi4"' cells decrease in the AIDS group, the percentage of CD14"^ monocytes did not change. In contrast, levels of soluble T cell antigens sCD4 and sCD8, which are higher in HIV-infected patients compared with normal subjects, showed no increase with disease progression. Serum levels of sCD14 were correlated positively with /ii-microglobulin levels (r^ = 0-63, P < 00001). Whereas the percentage of CD14^ monocytes did not change, an increase in monocytic CD14 expression in HIV-infected patients was observed {P < O'Ot). The percentage of a monocyte subset expressing both CD14 and CD16 increased from 6% in normal healthy•. ^^ 13% in HIVinfected patients (P < 0 001), and did not vary between the HIV patient ^ ^s. Incubation of cultured peripheral blood monocytes with azidothymidine had no effect on either normal or EPSinduced or IE-4-inhibited sCDI4 release in vitro. Therefore, an effect of AZT on sCD14 serum values in vivo is considered to be unlikely. Our data further provide evidence that monocytes/ macrophages are engaged in HIV infection.

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Monocyte antigen CD14 is a phospholipid anchored membrane protein

Cited by 56 publications

References 0 publications

Endotoxin activates human vascular smooth muscle cells despite lack of expression of CD14 mRNA or endogenous membrane CD14

Endotoxin activates human vascular smooth muscle cells despite lack of expression of CD14 mRNA or endogenous membrane CD14

Elevated levels of soluble CD14 in serum of patients with acute Plasmodium falciparum malaria

Increased soluble CD14 serum levels and altered CD14 expression of peripheral blood monocytes in HIV-infected patients

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