Biomedical subjects

Rolf Mentlein

Publications and source records attributed to Rolf Mentlein.

43 records · Page 3Linked to original sources

PubMed2002

Angiogenesis in fetal tendon development: spatial and temporal expression of the angiogenic peptide vascular endothelial cell growth factor.

In traction tendons, whose line of action corresponds to that of the muscle, few blood vessels are uniformly distributed within the tendon tissue. In gliding tendons, which change their direction of pull, an avascular zone is normally found in the region where the tendon wraps around the pulley. This avascular fibrocartilaginous gliding zone is predisposed for degenerative changes and spontaneous rupture. Since factors regulating angiogenesis in tendons are largely unknown, we analyzed the expression of the vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 (flt-1) and VEGFR-2 (KDR) in human fetal and adult tendon tissue by immunohistochemical, biochemical, and molecular biology methods. In order to elucidate whether mechanical stress might influence VEGF expression in tendon tissue we loaded primary cultures of rat tenocytes with intermittent hydrostatic pressure in a special cell culture chamber (amplitude: 0.2 Mpa, frequency: 0.1 Hz, time period: 5 h/day) and measured VEGF expression using ELISA. In fetal tendons high VEGF levels could be quantified by ELISA, whereas negligible ones were found in adult tissue. VEGF could be immunostained in tenocytes and endothelial cells. In the tibialis posterior tendon - as an example for a gliding tendon - VEGF immunostaining decreased in the gliding zone adjacent to the bony hypomochlion between week 20 and week 24 after gestation. This region remained largely avascular during the fetal period. In the peritendineum and in regions proximally and distally of the gliding zone immunostaining for VEGF was positive and factor VIII-positive microvessels could be detected. In these vessels, the VEGFR-1 (flt-1) and the VGEFR-2 could also be visualized. Reverse transcription-polymerase chain reaction (RT-PCR) confirmed the results regarding VEGF expression and showed further that the splice variants VEGF(121) and VEGF(165) are expressed exclusively during angiogenesis in fetal tendons. Monolayer cultures of tendon cells released measurable amounts of VEGF. Application of intermittent hydrostatic pressure decreased VEGF expression significantly. Thus, the angiogenic peptide VEGF is present in human fetal tendons, which are exposed to traction, but not in the avascular zone of gliding tendons, which are predominantly exposed to compressive and shearing forces. These findings support the view that the development of avascular zones in tendons might be caused by a mechanically induced downreglation of VEGF expression.

Achilles Tendon↗

PubMed2002

CD70/CD27 ligand, a member of the TNF family, is expressed in human brain tumors.

CD70 (CD27 ligand) has been implicated in proapoptotic signals mediated by its receptor CD27 in lymphocytes as well as in proliferative effects induced by reverse signaling in CD70-positive hematopoetic tumor cells. We were able to show that CD70 is expressed at the mRNA and protein level in human meningioma cells, glioma cells from solid human gliomas as well as glioma cell lines and 1 ependynoma. The intensity of CD70 expression varies considerably between different samples from 1 tumor type. In the U343 glioma cell line, CD70 was preferentially localized in the cell processes. Thus, our studies identify CD70 as a new marker molecule in brain tumors that are of nonhematopoetic origin.

Antigens, CD↗

PubMed2002

Vascular endothelial growth factor induces chemotaxis and proliferation of microglial cells.

Vascular endothelial growth factor (VEGF) is an angiogenic peptide that is produced in the brain after ischemia, injury or in malignant gliomas. Since these pathological conditions are associated with the infiltration of microglial cells, we investigated the expression of VEGF receptors (VEGFR) and possible effects of VEGF on cultivated microglial cells. As shown by reverse transcription-polymerase chain reaction and immunocytochemistry, rat microglial cells as well as the murine cell line BV-2 express the VEGFR-1, but not VEGFR-2. Murine VEGF induced 3H-thymidine incorporation into DNA of murine and rat microglial cells as well as chemotaxis in Boyden chamber assays. However, VEGF did not alter the phosphorylation of mitogen-activated protein kinases and only slightly that of the kinase Akt. These results show that microglial cells are targets for VEGF which induces migration and proliferation of these immunocompetent cells in the brain.

Animals↗

PubMed2002

Pleiotrophin, an angiogenic and mitogenic growth factor, is expressed in human gliomas.

Pleiotrophin (PTN) is a mitogenic/angiogenic, 15.3 kDa heparin-binding peptide that is found in embryonic or early postnatal, but rarely in adult, tissues. Since developmentally regulated factors often re-appear in malignant cells, we examined PTN expression in human glioma cell lines, cell cultures derived from solid gliomas and glioma sections. PTN mRNA or protein was detected by reverse transcriptase-polymerase chain reaction, immunohistochemistry, western blot or enzyme-linked immunoassay in all WHO III and IV grade gliomas and cells analyzed in vitro or in situ. One WHO II grade glioma investigated was PTN negative. In vitro, PTN was synthesized in perinuclear regions of glioma cells, secreted into the cultivation medium, but its production varied considerably between glioma cells cultivated from different solid gliomas or glioma cell lines. In situ, PTN expression was restricted to distinct parts/cells of the tumour. PTN did not influence the proliferation of glioma cells themselves, but stimulated [3H]thymidine incorporation into DNA of microglial cells. Furthermore, in Boyden chamber assays, PTN showed a strong chemotactic effect on murine BV-2 microglial cells. PTN is supposed to be a paracrine growth/angiogenic factor that is produced by gliomas and contributes to their malignancy by targeting endothelial and microglial cells.

Adult↗

PubMed2002

Dipeptidyl peptidase IV (CD26) on T cells cleaves the CXC chemokine CXCL11 (I-TAC) and abolishes the stimulating but not the desensitizing potential of the chemokine.

Dipeptidyl peptidase IV (DPP IV/CD26) is a costimulatory molecule as well as a protease highly expressed on T cells. Purified DPP IV has been recognized to inactivate peptide hormones, neuropeptides, and some chemokines by cleavage behind a proline residue at the penultimate N-terminal amino acid position. Here, we identified another substrate for DPP IV among the chemokine family: the interferon-inducible T cell alpha chemoattractant (I-TAC/CXCL11). Using a specific DPP IV inhibitor, we demonstrate that DPP IV is responsible for the cleavage of the chemokine by PHA/IL-2-treated T cells. As PHA/IL-2-treated T cells also express the CXCL11 receptor (CXCR3), we investigated whether truncation of CXCL11 would modulate its biological activity for these cells. Truncated CXCL11 [CXCL11(3-73)] had an eightfold reduced potential to bind and to regulate CXCR3, but was completely inactive in calcium flux and chemotaxis assays. However, consistent with its reduced but still considerable ability to down-regulate CXCR3, truncated CXCL11 desensitized T cell chemotaxis in response to the intact chemokine. Hence, CXCL11-induced T cell recruitment may be regulated by DPP IV-mediated proteolytic inactivation of CXCL11 and furthermore by desensitization of T cells via the degradation product CXCL11(3-73).

Calcium↗

PubMed2002

Animal model for the absorption of lipophilic substances from tear fluid by the epithelium of the nasolacrimal ducts.

PURPOSE: To compare the nasolacrimal tissues of several species to see how closely they resemble the human and to measure nasolacrimal absorption of a substance, to show that an absorption pathway exists for substances placed in the external eye, other than directly through the cornea or conjunctiva. METHODS: The nasolacrimal systems of six different vertebrates were investigated by light microscopy to find a species with a nasolacrimal system comparable to that of humans, for use in absorption experiments. In addition to primates, rabbits were revealed by histology to have a lacrimal system closely comparable to that of humans. The rabbit lacrimal system had a stratified epithelium consisting of two layers. Subepithelially, the lamina propria was composed of two strata: loose connective tissue containing elastic fibers and lymphatic cells and a rich venous plexus comparable to a cavernous body. Rabbits were therefore chosen for the absorption experiments. (3)H-cortisol was dropped into the eyes of female rabbits. After 21, 43, or 146 minutes, the rabbits were killed, the blood collected, and the nasolacrimal systems prepared and embedded for histologic examination. Serum was obtained from the clotted blood, and radioactivity was counted. Autoradiographs of sections of rabbit nasolacrimal duct were also prepared. RESULTS: Uptake of radioactivity into the serum was high and increased with time. After 21 minutes, maximum incorporation of the applied radioactivity into the blood the level was 7.1%; after 43 minutes, 12.4%; and after 146 minutes, 15.5%. Transport of radioactivity was visualized in autoradiographs of rabbit nasolacrimal systems. CONCLUSIONS: (3)H-cortisol is incorporated from the nasolacrimal ducts into the blood of rabbits. The comparable morphology of rabbits and humans suggests that absorption of cortisol would also take place in humans. Future investigations of the nasolacrimal passage are needed to understand whether absorption of normal tear fluid components in the nasolacrimal ducts is a physiological function that also plays a role in pathologic conditions such as dry eye. The similarities between rabbit and human nasolacrimal ducts support the use of the rabbit for such studies.

Absorption↗

PubMedDate not supplied

Functional significance of vascular endothelial growth factor receptor expression on human glioma cells.

Vascular endothelial growth factor (VEGF) is one of the most important angiogenesis factors. In many tumors, VEGF plays a pivotal role for their vascularization and is necessary to supply the malignant tissue with oxygen and nutrients. However, VEGF receptors (VEGFR) have recently been detected also on some tumor cells, and autocrine mitogenic effects of VEGF have been suspected. Since glioma cells are known to produce large amounts of VEGF, we investigated VEGFR-expression and effects of VEGF on glioma cells. The three glioma cell lines and eight glioma cells cultivated from WHO grade IV gliomas investigated strongly expressed VEGF121 and VEGF165, but weakly either VEGFR-1 or -2, sometimes for both, as evidenced by reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry. Quantitative RT-PCR revealed a 1000- to 50-fold lower expression of VEGFR than in cultivated human umbilical vein endothelial cells. In two glioma cell lines analyzed, VEGF induced a weak tyrosine phosphorylation of the VEGFR, but downstream signal transduction effects on the mitogen-activated protein kinases p42/p44 or transcription factors like AP-1 or NFKB were within the background of the methods. In accordance, VEGF or the VEGFR agonists VEGF-D or placenta growth factor (P1GF) did not produce significant effects on glioma cell proliferation or VEGF production. We conclude that despite a low expression of VEGFR in some glioma cells functional effects are low and autocrine growth stimulatory effects within a glioma are minor.

Angiogenesis Inducing Agents↗