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Biomedical subjects

M Hartmann

Publications and source records attributed to M Hartmann.

At least 109 records · Page 6Linked to original sources
PubMed1998

Comparison of tissue oxygen-tension measurements by different devices. An experimental study in pigs.

UNLABELLED: The aim of this study was to evaluate measurements of subcutaneous oxygen tension (PscO2) generated by three different monitors and to compare measurements obtained with and without the tonometer technique in a standardized animal model. Seven domestic pigs weighing 20-28 kg were anaesthetized and mechanically ventilated. A pulmonary artery catheter was inserted for haemodynamic monitoring and temperature measuring. An external carotid artery was cannulated for blood pressure monitoring and blood sampling. A peripheral venous line was used for fluid and drug infusion. The animals were then subjected to hyperoxia and hypoxia by varying the inspiratory oxygen fractions (FiO2) between 0.1 and 0.8. Arterial and central venous blood gases were analysed at each step of FiO2. Cardiac output was determined using a thermodilution technique. Central, subcutaneous and skin surface temperatures were measured. Three different devices for subcutaneous tissue oxygen-tension (PscO2) measurements were compared: (1) Biogenesis, (2) Continucath and (3) Paratrend 7. Continucath was used both with and without tonometer simultaneously. Inter Class Coefficient of Correlation between PscO2 values obtained by the two Continucath sensors was 76% and between Paratrend 7 and Biogenesis 88%. Absolute values generated by Biogenesis and Paratrend 7 were not different. PscO2 values obtained with the Continucath devices were on average 50% higher than those generated by Biogenesis and Paratrend 7 (p < 0.05). CONCLUSIONS: The new Paratrend 7 and the old Biogenesis sensors generate almost equal tissue oxygen-tension values in response to changes in arterial oxygen tension. The Continucath sensor generates almost 50% higher values compared with the Paratrend 7 and Biogenesis sensors, both with and without tonometer.

Animals↗
PubMed1998

Local fibrinolysis and aspiration of intracerebral hematomas in rats. An experimental study using MR monitoring.

Serial magnetic resonance (MR) imaging has not yet been validated in the therapy of experimental intracerebral hematomas in a rat model. It is possible to test the effect of local fibrinolysis and aspiration on the clot volume using serial magnetic resonance imaging and different MR-sequences. Experiments were carried out in 22 male Sprague-Dawley rats. Intracerebral hematoma was produced by injection of fresh autologous blood into the caudate nucleus using a double injection technique. Thirty minutes later 10 rats were treated by injecting 12 microliters of recombinant tissue plasminogen activator. MR-imaging was performed immediately after generation of the hematoma and after clot lysis. The clot volume measured in the magnetic resonance images was compared with that obtained in stained histological serial sections at the end of the experiment. Serial MR scanning demonstrated a significant reduction (p < 0.01) of hematoma volume after fibrinolysis followed by aspiration of the blood clot. The best correlation between MR- and histological volumetry was found on RF-spoiled FLASH 2D-images. This study documents the efficacy of MRI in detecting and delineating the size of acute intracerebral hematomas and its time course. Local fibrinolysis and aspiration can be simulated in an experimental rat model.

Animals↗
PubMed1998

Disturbance of DNA damage recognition after UV-irradiation by nickel(II) and cadmium(II) in mammalian cells.

Nickel(II) and cadmium(II) have been shown previously to inhibit the incision step of nucleotide excision repair. By applying a gel-mobility-shift assay and HeLa nuclear extracts the effect of both metals on the damage recognition step of the repair process was investigated. Two proteins of 34 and 40 kDa were identified that bind with high affinity to a UV-irradiated synthetic oligonucleotide. When applying nuclear extracts from HeLa cells treated with 50 microM nickel(II) and higher, there was a dose-dependent decrease in protein binding; this effect was largely reversible by the addition of magnesium(II) to the binding reaction. In the case of cadmium(II), a dose-dependent inhibition of DNA-protein interactions was detected at 0.5 microM and higher, which was almost completely reversible by the addition of zinc(II). Therefore, compounds of both metals disturb DNA-protein interactions essential for the initiation of nucleotide excision repair most likely by the displacement of essential metal ions.

Binding Sites↗
PubMed1998

Pharmacokinetics of pantoprazole in patients with end-stage renal failure.

BACKGROUND: Pantoprazole is a selective inhibitor of the gastric H+/K+-ATPase with a low potential to interact with the cytochrome P450 enzyme system. Since pantoprazole is metabolized in the liver to metabolites which are mainly cleared by the renal route, it was the aim of this study to investigate its pharmacokinetics in patients with end-stage renal failure undergoing regular haemodialysis. METHODS: Eight patients with end-stage renal failure (creatinine clearance < 5 ml/min, age 45-65 years) on regular haemodialysis (duration of haemodialysis 4-5 h, cuprophan-dialyser Hemoflow E3, surface 1.3 m2) were given single i.v. doses of 40 mg pantoprazole one day before haemodialysis (A) and on a haemodialysis day immediately before the start of the haemodialysis (B). Concentrations of pantoprazole and metabolite M2 were determined in plasma and urine over 24 h and in timed samples of the dialysis fluid by HPLC. The protein binding was determined using equilibrium dialysis. RESULTS: The pharmacokinetic characteristics of pantoprazole AUC, t(1/2), CL and V(d area) (geometric means) were 2.4 mgxh/l, 0.63 h, 0.227 l/h/kg and 0.206 l/kg on day A (without dialysis) and 2.3 mgxh/l, 0.8 h, 0.237 l/h/kg and 0.273 l/kg on day B (with dialysis), respectively. The protein binding was 96%. Pantoprazole was found in small amounts in the dialysis fluid (max. 2.1% of the dose) but not in the urine. Pantoprazole was well tolerated. In particular, there were no clinically relevant changes in blood count, electrolytes or liver enzymes. CONCLUSIONS: Haemodialysis has no influence on the pharmacokinetic characteristics of pantoprazole. Thus, pantoprazole is not dialysed to any relevant degree, and therefore no dose-adjustment is required for patients with end-stage renal failure undergoing regular haemodialysis treatment.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

Beta interferon is produced by Chlamydia trachomatis-infected fibroblast-like synoviocytes and inhibits gamma interferon-induced HLA-DR expression.

Infection of fibroblast-like synovial cells with Chlamydia trachomatis (serotype D strain IC Cal 8) in culture induced the secretion of beta interferon (IFN-beta). Chlamydial infection inhibited IFN-gamma-induced expression of HLA-DR antigen in the cells. Addition of IFN-beta antibody directly to infected cultures mitigated HLA-DR inhibition, suggesting involvement of produced IFN-beta.

Cells, Cultured↗
PubMed1998

The central, surface-exposed region of the flagellar hook protein FlgE of Campylobacter jejuni shows hypervariability among strains.

In a previous study, we observed that monoclonal antibodies raised against the hook protein FlgE of Campylobacter jejuni LIO 36, isolate 5226, bound exclusively to this strain. The aim of this study was to elucidate the molecular basis for these binding specificities. The hook protein-encoding gene flgE of C. jejuni was cloned in Escherichia coli and sequenced. The flgE genes of four additional C. jejuni strains were amplified by PCR and also sequenced. Comparison of the deduced amino acid sequences revealed a high degree of variability in the central parts of the FlgE proteins among the strains, including variable and hypervariable domains. These findings may indicate a selective pressure of C. jejuni hosts, forcing the bacteria to generate variations in surface-exposed antigenic determinants.

Amino Acid Sequence↗
PubMed1998

Differences in pH-dependent activation rates of substituted benzimidazoles and biological in vitro correlates.

Gastric proton pump inhibitors (PPIs) are substituted benzimidazole prodrugs that require an acid-induced activation. Its rate depends on the reactivity of the molecule relative to the environmental pH and determines the drug's tissue selectivity. Factors affecting the exposure of moderately acidic tissues to the activated PPI are the area under the serum concentration-time curve (AUC), serum protein binding, the partition coefficient logP and the serum elimination half-life relative to the chemical activation half-life at a critical tissue pH of about 5. These parameters have therefore been determined in a comparative fashion in the present study. The data shows that pantoprazole is less likely to undergo unwanted activation at moderately acidic targets as opposed to the parietal cell, compared to omeprazole. Actually, although 40 mg pantoprazole (steady state) gave a slightly higher serum AUC of the total parent compound than 40 mg omeprazole (10.5 vs. 7.1 micromol x h x l[-1]), a higher serum protein binding of pantoprazole versus omeprazole (98 vs. 96%) reversed the AUC values for the free drug in favor of a lower value for pantoprazole (0.19 vs. 0.28 micromol x h x l[-1]). It is the free parent compound that equilibrates across cell membranes to be activated in acidic tissue compartments. At pH 5.1, the activation half-life of pantoprazole was 4.7 versus 1.4 h for omeprazole, the latter being in the order of the common serum elimination half-life determined in an intraindividual comparison (1.24 vs. 1.25 h). Thus, pantoprazole is eliminated faster from blood than it is activated at a pH of about 5, while omeprazole is as quickly activated at this pH as it is eliminated from blood. Biological in vitro experiments confirmed that pantoprazole displays a lower liability to interfere with unwanted biological targets. This has been demonstrated in vitro for inhibition of both renal Na+/K+-ATPase, lysosomal acidification and the production of reactive oxygen species by neutrophils.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

Pantoprazole does not interact with the pharmacokinetics of carbamazepine.

OBJECTIVE: Pantoprazole is a H+/K+-ATPase inhibitor with a minimized potential of interaction with the cytochrome P450 system. Imidazole derivatives such as cimetidine and omeprazole have been shown to markedly interact with carbamazepine, a major anticonvulsant with a narrow therapeutic range. Therefore, the influence of steady-state pantoprazole on the pharmacokinetics of carbamazepine was investigated. SUBJECTS AND METHODS: N = 20 healthy volunteers (12 male/8 female) completed a double-blind, placebo-controlled, randomized crossover study. During the test period they received 40 mg pantoprazole p.o. once daily for 11 days and concomitantly a single oral dose of 400 mg carbamazepine on day 5. In the reference period placebo was administered instead of pantoprazole. RESULTS: Serum concentrations of carbamazepine and its active metabolite carbamazepine-10,11-epoxide were measured until day 11. Geometric means of AUC (extent characteristic) and Cmax/AUC (rate characteristic) of carbamazepine were 292 and 287 mgxh/l, and 0.0150 and 0.0144 l/h (reference and test), respectively. Point estimates and 90% confidence intervals of the ratios were 0.98 (0.95, 1.01) for AUC, and 0.96 (0.92, 1.00) for Cmax/AUC, respectively. Since the 90% confidence intervals of the primary characteristics, AUC and Cmax/AUC were entirely within the predefined equivalence range of 0.80 - 1.25, lack of interaction of pantoprazole with the pharmacokinetics of carbamazepine was demonstrated. Equivalence was also demonstrated for carbamazepine-10,11-epoxide using the characteristics AUC and Cmax. CONCLUSION: No dose adjustment of carbamazepine is therefore required during concomitant treatment with pantoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

Secretion of cytokines by human synoviocytes during in vitro infection with Chlamydia trachomatis.

OBJECTIVE: Since Chlamydia-induced reactive arthritis is associated with the presence of viable chlamydiae in the synovial membrane, we studied the ability of Chlamydia trachomatis to stimulate a cytokine response by fibroblast-like synoviocytes in culture. METHODS: Fibroblast-like cells derived from biopsies of the synovial membrane were infected with Chlamydia trachomatis serotype E. Interleukin-6 (IL-6), transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha) were determined using bio-assays. Granulocyte macrophage colony stimulating factor (GMCSF) was quantified by ELISA. RESULTS: Fibroblast-like synovial cells were capable of supporting chlamydial growth in vitro. Chlamydia trachomatis stimulated synoviocytes to produce IL-6, TGF-beta, and GMCSF. IL-1beta increased the production of IL-6 and GMCSF by mock-infected and infected cells. Treatment of synoviocytes with interferon-gamma resulted in the release of TNF-alpha in response to chlamydial infection. CONCLUSION: Chlamydia-induced cytokine release from synovial fibroblasts may contribute to alterations in the synovial membrane promoting the development of joint inflammation.

Bacteria↗
PubMed1997

Production of a recombinant antithrombotic and fibrinolytic protein, PLATSAK, in Escherichia coli.

The three main components involved in thrombosis and haemostasis are thrombin, platelets, and plasmin. Almost all inhibitors of thrombosis are focused either on the inhibition of thrombin or on the inhibition of platelets. We designed a construct using the fibrinolytic activity of staphylokinase, fused via a cleavable linker to an antithrombotic peptide of 29 amino acids. The peptide was designed to include three inhibitory regions: (1) the Arg-Gly-Asp (RGD) amino acid sequence to prevent fibrinogen binding to platelets; (2) a part of fibrinopeptide A, an inhibitor of thrombin; and (3) the tail of hirudin, a potent direct antithrombin. The amino acid sequence of the 29 amino acid peptide was reverse translated, and the gene was chemically synthesised and cloned into an expression vector as a 3' fusion to the staphylokinase gene. Gene expression was induced in E. coli Top 10 cells and the fusion protein, designated PLATSAK, was purified using metal affinity chromatography. The purified fusion protein significantly lengthened the activated partial thromboplastin time and thrombin time and inhibited the amidolytic activity of thrombin. The fibrinolytic activity was almost equal to that of recombinant staphylokinase as measured with a thrombelastograph. Platelet aggregation was not markedly inhibited by PLATSAK, probably due to the unfavourable three dimensional structure, with the Arg-Gly-Asp sequence buried inside. Our results confirm that it is feasible to design and produce a hybrid multifunctional protein that targets various components of the haemostatic process.

Amino Acid Sequence↗
PubMed1997

Radiotherapy in stage IIA and IIB testicular seminoma with reduced portals: a prospective multicenter study.

PURPOSE: A prospective multicenter study was carried out to estimate the treatment outcome of radiotherapy in Stage II seminoma after the application of modern staging and radiotherapy techniques. The lower margin of the iliac field was positioned on the upper rim of the acetabulum to reduce the amount of scattered irradiation to the remaining testicle. METHODS AND MATERIALS: The study was carried out in 25 centers in Germany. Patients with pure seminoma, negative AFP-values, and retroperitoneal lymph node metastases of less than 5 cm in diameter were entered into the study. All patients received a ventrodorsal opposed field irradiation of the para-aortic and the ipsilateral iliac lymph nodes. The fields extended from the top of the 11th thoracic vertebra to the top of the acetabulum. Patients in Stage IIA (lymph nodes <2 cm ) received 30 Gy, and patients with Stage IIB (lymph nodes between 2 and 5 cm) 36 Gy total dose. RESULTS: 39 patients in Stage IIA and 19 patients in Stage IIB were evaluated. After a median observation time of 37 months all patients are alive and disease free. Recurrence free survival in stage IIA was 100%. Two patients in Stage IIB experienced a recurrence 10 and 17 months after the end of radiotherapy. The actuarial recurrence free survival estimate in Stage IIB was 94.1% for 1 year and 87.4% for 2 years. One recurrence in Stage IIB occurred in the mediastinum, one in the mediastinum, and one the lung. Both patients could be salvaged by chemotherapy. There were no pelvic recurrences. The treatment was well tolerated, with nausea being the most common side effect (56.9% Grade 1, 15.5% Grade 2, and 8.6% Grade 3). Diarrhea occurred in 15.5% (Grade 1), 15.5% (Grade 2), and 5.2% (Grade 3) of the patients. CONCLUSIONS: The outcome of para-aortic and ipsilateral iliac irradiation in Stage IIA/B testicular seminoma is excellent with the currently available staging methods and treatment facilities. The treatment is well tolerated. The lower margin of the iliacal field can be placed at the acetabulum.

Adult↗
PubMed1997

Design of low molecular weight hematoregulatory agents from the structure-activity relationship of a dimeric pentapeptide.

We report herein, a new class of simple hematoregulatory semipeptides, formally derived from the cystine-dimerized peptide pGlu-Glu-Asp-Cys-Lys-OH, where the disulfide bond has been replaced by an isosteric dicarba bridge. The structure-activity relationship (SAR) of a series of analogues incorporating replacements at positions 1 and 2 of peptide 1 led to the design of active conformationally constrained cyclic peptides (12, 13). Ring closure was achieved by cyclization of the N-terminal amino groups at position 2 of peptide 2 using pyrazine-2,3-dicarboxylic acid. Subsequent excision of the putative C-terminal scaffold domain from the active cyclic peptides resulted in the discovery of a new class of low molecular weight hematoregulatory agents exemplified by compound 16. This semipeptide analogue, comprising two D-Ser residues connected via amide bonds to the acid groups of pyrazine-2,3-dicarboxylic acid, had comparable biological activity to the lead peptide 1. The stereochemical requirements for the observed biological activity of these novel compounds were examined. Furthermore, the hematopoietic synergistic activity induced by compound 16 in stromal cell cultures was blocked by an antibody known to neutralize the hematoregulatory effect of 1, indicating a common mechanistic end point. Compounds of the class typified by 16 may form the basis for the development of novel therapeutic agents within the area of immunoregulation.

Amino Acid Sequence↗
PubMed1997

Preferential expression of novel MUC1 tumor antigen isoforms in human epithelial tumors and their tumor-potentiating function.

The human MUC1 gene expresses at least 2 type 1 membrane proteins: MUC1/REP, a polymorphic high m.w. MUC1 glycoprotein often highly expressed in breast cancer tissues and containing a variable number of tandem 20 amino acid repeat units, and the MUC1/Y protein, which lacks this repeat array and, therefore, is not polymorphic. Despite their documented importance in signal transduction processes, the relative expression of the 2 isoforms in epithelial tumors is unknown. Using antibody reagents which recognize different MUC1 domains, the expression of these isoforms in malignant epithelial cells has been evaluated. A comparison of the amounts of the 2 isoforms revealed preferential expression of the novel MUC1/Y protein in breast cancer tissue samples. Furthermore, although the MUC1/REP protein is almost undetectable in HeLa cervical adenocarcinoma epithelial cells, the MUC1/Y isoform is extensively expressed in these cells. The presence of the MUC1/Y sequence as well as that of an additional tandem-repeat-array-lacking isoform, designated MUC1/X, were demonstrated by reverse transcriptase PCR amplification of RNA extracted from HeLa and ovarian carcinoma cells. It has been shown previously that the MUC1 cytoplasmic domain interacts with the SH2 domain containing GRB2 protein, which transduces signals to ras, a protein which in its activated form can lead to cell transformation. We present here data demonstrating that MUC1/Y isoform expression increases the tumorigenic potential of DA3 mouse mammary epithelial cells; in contrast, potentiation of tumorigenicity is not observed with MUC1/REP expression. Our studies thus demonstrate that expression of the MUC1 gene in epithelial tumors can give rise to substantial levels of MUC1 proteins devoid of the tandem repeat array, which are generated by alternative splicing mechanisms.

Amino Acid Sequence↗
PubMed1997

Myeloid-related protein (MRP) 8 and MRP14, calcium-binding proteins of the S100 family, are secreted by activated monocytes via a novel, tubulin-dependent pathway.

Myeloid-related protein (MRP) 8 and MRP14, two members of the S100 family expressed in myelomonocytic cells, have been ascribed some extracellular functions, e.g. antimicrobial, cytostatic, and chemotactic activities. Since S100 proteins lack structural requirements for secretion via the classical endoplasmic reticulum/Golgi route, the process of secretion is unclear. We now demonstrate the specific, energy-dependent release of MRP8 and MRP14 by human monocytes after activation of protein kinase C. This secretory process is not blocked by inhibitors of vesicular traffic through the endoplasmic reticulum and Golgi, and comparative studies on tumor necrosis factor-alpha and interleukin-1beta indicate that MRP8 and MRP14 follow neither the classical nor the interleukin-1-like alternative route of secretion. Inhibition by microtubule-depolymerizing agents revealed that MRP8/MRP14 secretion requires an intact tubulin network. Accordingly, upon initiation of MRP8/MRP14 secretion, immunofluorescence microscopy showed a co-localization of both proteins with tubulin filaments. Release of MRP8 and MRP14 is associated with down-regulation of their de novo synthesis, suggesting that extracellular signaling via MRP8/MRP14 is restricted to distinct differentiation stages of monocytes. Our data provide evidence that the S100 proteins MRP8 and MRP14 are secreted after activation of protein kinase C via a novel pathway requiring an intact microtubule network.

Antigens, Differentiation↗
PubMed1997

Staphylokinase requires NH2-terminal proteolysis for plasminogen activation.

Staphylokinase (Sak), a single-chain protein comprising 136 amino acids with NH2-terminal sequence,SSSFDKGKYKKGDDA forms a complex with plasmin, that is endowed with plasminogen activating properties. Plasmin is presumed to process mature (high molecular weight, HMW) Sak to low molecular weight derivatives (LMW-Sak), primarily by hydrolyzing the Lys10-Lys11 peptide bond, but the kinetics of plasminogen activation by HMW-Sak and LMW-Sak are very similar. Here, the requirement of NH2-terminal proteolysis of Sak for the induction of plasminogen activating potential was studied by mutagenesis of Lys10 and Lys11 in combination with NH2-terminal microsequence analysis of equimolar mixtures of Sak and plasminogen and determination of kinetic parameters of plasminogen activation by catalytic amounts of Sak. Substitution of Lys10 with Arg did not affect processing of the Arg10-Lys11 site nor plasminogen activation, whereas substitution with His resulted in cleavage of the Lys11-Gly12 peptide bond and abolished plasminogen activation. Substitution of Lys11 with Arg did not affect Lys10-Arg11 processing or plasminogen activation, whereas replacement with His did not prevent Lys10-His11 hydrolysis but abolished plasminogen activation. Substitution of Lys11 with Cys yielded an inactive processed derivative which was fully activated by aminoethylation. Deletion of the 10 NH2-terminal amino acids did not affect plasminogen activation, but additional deletion of Lys11 eliminated plasminogen activation. Thus generation of plasminogen activator potential in Sak proceeds via plasmin-mediated removal of the 10 NH2-terminal amino acids with exposure of Lys11 as the new NH2 terminus. This provides a structural basis for the hypothesis, derived from kinetic measurements, that plasminogen activation by Sak needs to be primed by plasmin and a mechanism for the high fibrin selectivity of Sak in a plasma milieu.

Amino Acid Sequence↗
PubMed1997

Recognition of chlamydial antigen by HLA-B27-restricted cytotoxic T cells in HLA-B*2705 transgenic CBA (H-2k) mice.

OBJECTIVE: The association of reactive arthritis (ReA) with HLA-B27 and the presence of bacterial antigen in joints with ReA suggest that bacterial peptides might be presented by the HLA-B27 molecule and thus stimulate CD8 T cells. This study was performed to investigate the B27-restricted cytotoxic T lymphocyte (CTL) response to Chlamydia trachomatis, using the model of HLA-B27 transgenic mice. METHODS: CBA (H-2k) mice homozygous for HLA-B*2705 and human beta2-microglobulin expression were immunized with C trachomatis or with the chlamydial 57-kd heat-shock protein (hsp57) coupled to latex beads. Cytotoxicity of lymphocytes from in vivo-primed transgenic mice was tested against C trachomatis-infected targets. Blocking experiments were performed with monoclonal antibodies (MAb) against class I major histocompatibility complex molecules. RESULTS: A Chlamydia-specific lysis of both B27-transfected and nontransfected target cells was observed. This response could be inhibited by anti-B27 and anti-H2 MAb. CTL from mice immunized with hsp57 were not able to lyse Chlamydia-infected target cells, and Chlamydia-specific CTL could not destroy targets loaded with hsp57. CONCLUSION: These results suggest the existence of at least 2 CTL populations in this mouse model: one recognizing peptide of bacteria-infected cells restricted by HLA-B*2705 and the other recognizing peptide of bacteria-infected cells restricted by the murine H-2Kk molecule. It does not appear that hsp57 is a major target for the CD8 T cell response directed against Chlamydia. This animal model opens the way for identifying bacterial epitopes presented by HLA-B27, and might thus help to clarify the pathogenesis of B27-associated diseases.

Animals↗
PubMed1997

Endothelial cells in chorionic fetal vessels of first trimester placenta express HLA-G.

Using four different HLA-G-recognizing monoclonal antibodies (mAb), we investigated whether this nonclassical HLA class I molecule could be expressed in placental cell types other than extravillous cytotrophoblasts (evct) in which HLA-G has already been detected. Immunohistochemical analysis was performed on serial cryosections of first trimester placenta as well as on maternal decidual tissue. In addition to some proliferative evct, the recently described BFL.1 mAb also slightly stained some villous cytotrophoblast (vct) stem cells located near cell columns and cell islands, which until now have been considered as HLA-G negative. The same staining pattern was obtained with the 16G1 mAb raised against the soluble HLA-G isoform, whereas neither 87G nor HCA2 reacted with vct but did strongly label the invasive populations of evct, including interstitial and endovascular trophoblasts. Surprisingly, BFL.1 strongly and reproducibly stained endothelial cells in the fetal capillaries present in the mesenchymal core of the chorionic villi, whereas none of the other surrounding cellular components were stained. The same specific labeling was obtained, although with less intensity, with the three other HLA-G-recognizing mAb. In contrast, maternal endothelial cells present in spiral arteries of the decidua parietalis remained unstained. This unexpected cellular localization suggests that HLA-G may be present as a soluble form during the whole period of fetal vascularization and/or exert a nonimmunological function related to the endothelial cell type, in particular in the angiogenesis process which is highly active, until term, in chorionic villi.

Blood Vessels↗