β2-Glycoprotein-I mRNA Transcripts Are Expressed by Hepatocytes but not by Resting or Activated Human Endothelial Cells

Barrera, Claudia Alvarado-de la; Bahena, Susana; Llórente, Luis; Martínez-Castillo, Araceli; Alarcón‐Segovia, Donato; Cabral, Antonio R.

doi:10.1016/s0049-3848(98)00069-3

Cited by 7 publications

(4 citation statements)

References 15 publications

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“…Although it is generally accepted that the protein is present on different endothelial cell membranes (50,51), the results on apoH mRNA expressed by endotheliocytes are conflicting (39,40). Moreover, we did not observe apoH transcripts in endothelial cells.…”

Section: Discussioncontrasting

confidence: 78%

RT-PCR and in situ hybridization analysis of apolipoprotein H expression in rat normal tissues

Ragusa

Costa²,

Cefalù³

et al. 2006

Int J Mol Med

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Abstract. In this study, by using different techniques (i.e. Northern blot hybridization, RT-PCR and Southern blot hybridization) on various normal rat tissues, we were able to identify liver, kidney, heart, small intestine, brain, spleen, stomach and prostate as tissues in which the ApoH gene is transcribed. Moreover, for some of these tissues, by in situ hybridization, we found a specific localization of apoH transcripts. For instance epithelial cells of the bile ducts in liver and of the proximal tubules in kidney are the major sites of apoH synthesis. Our data suggest that some of the different physiological roles proposed for apoH could correlate with its direct expression, while others could correlate with its absorption from bloodstream or adjacent cells.

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Section: Discussioncontrasting

confidence: 78%

RT-PCR and in situ hybridization analysis of apolipoprotein H expression in rat normal tissues

Ragusa

Costa²,

Cefalù³

et al. 2006

Int J Mol Med

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“…The origin and function of ␤ 2 GP1 at the cell surface and in late endosomes remain to be established. Only two studies have addressed the expression of ␤ 2 GP1 by EC; one detected ␤ 2 GP1 mRNA the other did not (12,26). The observation that ␤ 2 GP1 starvation strongly reduces anti-␤ 2 GP1 antibody binding to HUVEC (16,26) suggests that most HUVEC-associated ␤ 2 GP1 is derived from the culture medium.…”

Section: Discussionmentioning

confidence: 99%

“…Only two studies have addressed the expression of ␤ 2 GP1 by EC; one detected ␤ 2 GP1 mRNA the other did not (12,26). The observation that ␤ 2 GP1 starvation strongly reduces anti-␤ 2 GP1 antibody binding to HUVEC (16,26) suggests that most HUVEC-associated ␤ 2 GP1 is derived from the culture medium. Our findings of a continuous presence of ␤ 2 GP1 in EC cultivated in the absence of serum, implies either a production of ␤ 2 GP1 by EC or a low turnover of ␤ 2 GP1.…”

Section: Discussionmentioning

confidence: 99%

Localization of β2-Glycoprotein 1 in Late Endosomes of Human Endothelial Cells

Dunoyer‐Geindre¹,

Kruithof²,

Rochemonteix³

et al. 2001

Thromb Haemost

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SummaryAntiphospholipid antibodies (APLA) are associated with thrombophilia and recurrent pregnancy loss. Different mechanisms have been proposed to explain their pathogenic effects and among them, we have previously shown that APLA accumulate in late endosomes of human umbilical vein endothelial cells (HUVEC) leading to a redistribution of the cation-independent mannose-6-phosphate receptor (CI-M6PR). Because many APLA are directed towards β2-glycoprotein 1 (β2GP1)-phospholipid complexes, we investigated the localisation of β2GP1 in HUVEC. By immunofluorescence analysis, using monoclonal and polyclonal anti- β2GP1 antibodies, we detected β2GP1 at the cell surface and in late endosomes. Incubation of HUVEC with anti- β2GP1 antibodies resulted in antibody accumulation at the cell surface and within late endosomes and in a redistribution of the CI-M6PR from the Golgi apparatus to late endosomes. The anti- β2GP1 antibodies remained detectable in late endosomes even after several days of incubation in antibody-free medium. The accumulation of anti- β2GP1 antibodies in late endosomes of endothelial cells and the resulting modification of intracellular protein trafficking may contribute to the pathogenic effects of these antibodies.

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“…Now, the issue of the origin of b2-gpI displayed on the endothelial surface. Synthesis within the ECs is unlikely, because were that to be case, transcripts for b2-gpI should have been detected by all investigators (12,13). Therefore, the protein must derive from the circulation, although its affinity for plasma membrane-resembling PL preparations is relatively low (14).…”

mentioning

confidence: 99%

TLR2 Is One of the Endothelial Receptors for β2-Glycoprotein I

Alard

Gaillard

Daridon

et al. 2010

The Journal of Immunology

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During the antiphospholipid syndrome, β2-gpI interacts with phospholipids on endothelial cell (EC) surface to allow the binding of autoantibodies. However, induced-pathogenic intracellular signals suggest that β2-gpI associates also with a receptor that is still not clearly identified. TLR2 and TLR4 have long been suspected, yet interactions between TLRs and β2-gpI have never been unequivocally proven. The aim of the study was to identify the TLR directly involved in the binding of β2-gpI on EC surface. β2-gpI was not synthesized and secreted by ECs in vitro, but rather taken up from FCS. This uptake occurred through association with TLR2 and TLR4 which partitioned together in the lipid rafts of ECs. After coimmunoprecipitation, mass-spectrometry identification of peptides demonstrated that TLR2, but not TLR4, was implicated in the β2-gpI retention. These results were further confirmed by plasmon resonance-based studies. Finally, siRNA were used to obtain TLR2-deficient ECs that lost their ability to bind biotinylated β2-gpI and to trigger downstream phosphorylation of kinases and activation of NFκB. TLR4 may upregulate TLR2 expression, thereby contributing to β2-gpI uptake. However, our data demonstrate that direct binding of β2-gpI on EC surface occurs through direct interaction with TLR2. Furthermore, signaling for anti–β2-gpI may be envisioned as a multiprotein complex concentrated in lipid rafts on the EC membrane.

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β2-Glycoprotein-I mRNA Transcripts Are Expressed by Hepatocytes but not by Resting or Activated Human Endothelial Cells

Cited by 7 publications

References 15 publications

RT-PCR and in situ hybridization analysis of apolipoprotein H expression in rat normal tissues

RT-PCR and in situ hybridization analysis of apolipoprotein H expression in rat normal tissues

Localization of β2-Glycoprotein 1 in Late Endosomes of Human Endothelial Cells

TLR2 Is One of the Endothelial Receptors for β2-Glycoprotein I

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