Effect of Recombinant Tumor Necrosis Factor-Alpha on Cultured Microvascular Endothelial Cells Derived From Human Dermis

Detmar, Michael; Imcke, E.; Ruszczak, Z; Orfanos, Constantin E.

doi:10.1111/1523-1747.ep12875807

Cited by 38 publications

(15 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ECs in vivo are commonly thought to express MHC class II only after encounter of proinflammatory cytokines. [21][22][23][24] As a major example for environment-dependent gene expression, we find that nonactivated BECs in vivo, but not LECs, express prominently the full repertoire of gene products that are required for MHC class II-dependent antigen presentation. It is highly unlikely that MHC class II expression on BECs is due to the procedure of EC isolation because immunohistochemistry on fresh, snap-frozen human skin revealed substantial MHC class II expression on BECs.…”

Section: Discussionmentioning

confidence: 83%

Blood and lymphatic endothelial cell-specific differentiation programs are stringently controlled by the tissue environment

Amatschek

Kriehuber

Bauer

et al. 2007

Blood

123

101

View full text Add to dashboard Cite

The discovery of marker proteins of human blood (BECs) and lymphatic endothelial cells (LECs) has allowed researchers to isolate these cells. So far, efforts to unravel their transcriptional and functional programs made use of cultured cells only. Hence, it is unknown to which extent previously identified LEC-and BEC-specific programs are representative of the in vivo situation. Here, we define the human BEC-and LEC-specific in vivo transcriptomes by comparative genomewide expression profiling of freshly isolated cutaneous EC subsets and of non-EC skin cells (fibroblasts, mast cells, dendritic cells, epithelial cells). Interestingly, the expression of most of the newly identified EC subset-discriminating genes depends strictly on the in vivo tissue environment as revealed by comparative analyses of freshly isolated and cultured EC subsets. The identified environment-dependent, EC subsetrestricted gene expression regulates lineage fidelity, fluid exchange, and MHC class II-dependent antigen presentation.As an example for a BEC-restricted in vivo function, we show that non-activated BECs in situ, but not in vitro, assemble and display MHC class II protein complexes loaded with self-peptides. Thus, our data demonstrate the key importance of using precisely defined native IntroductionThe microvasculature is actively involved in metabolism and immune cell trafficking. Although the supply with oxygen and nutrients as well as the attraction of leukocytes is accomplished by blood vessels, the removal of extracellular fluid from the tissues and the guidance of immune cells to lymph nodes are carried out by lymphatic vessels. At the molecular level, these different functional capabilities are likely encoded by the transcriptional repertoires of blood vessel endothelial cells (BECs) and lymphatic ECs (LECs). Recently, the discovery of the LEC-specific marker proteins podoplanin (PDPN) and LYVE-1 allowed researchers to isolate and propagate BECs and LECs in vitro. 1,2 Accordingly, several techniques, including genomewide expression profiling coupled to bioinformatic approaches, have been used to identify the spectrum of genes that are expressed in cultured LECs and BECs. [3][4][5][6] However, probably as a result of technical limitations, genomewide analyses were not performed on freshly isolated ECs. Thus, it is possible that ECs, in their tissue-resident state, have a transcriptional and, thus, functional repertoire that differs from that of cultured ECs. In fact, the specialized ECs of high endothelial venules rapidly lose EC subset-defining antigen expression and morphology when these cells were placed in culture. 7 This supports that active signal exchange between ECs and the local tissue environment can also be of critical importance for the maintenance of differentiation and function of LECs and BECs.To address whether and, if so, to which extent tissue-resident LECs or BECs resemble their cultured counterparts, we established for the first time the complete transcriptomes of freshly isolated cutaneous LECs, BECs, a...

show abstract

Section: Discussionmentioning

confidence: 83%

Blood and lymphatic endothelial cell-specific differentiation programs are stringently controlled by the tissue environment

Amatschek

Kriehuber

Bauer

et al. 2007

Blood

123

101

View full text Add to dashboard Cite

show abstract

“…Human dermal microvascular EC were isolated from neonatal foreskins (29,30) and cultured as described (25). For experiments involving Northern blot analysis, cells were shifted to EC basal medium (Clonetics, San Diego, CA) supplemented with 2% fetal calf serum and antibiotics 24 h prior to stimulation with VEGF.…”

Section: Methodsmentioning

confidence: 99%

Angiogenesis promoted by vascular endothelial growth factor: Regulation through α₁β₁and α₂β₁integrins

Senger

Claffey

Benes

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

495

349

View full text Add to dashboard Cite

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is a cytokine of central importance for the angiogenesis associated with cancers and other pathologies. Because angiogenesis often involves endothelial cell (EC) migration and proliferation within a collagen-rich extracellular matrix, we investigated the possibility that VEGF promotes neovascularization through regulation of collagen receptor expression. VEGF induced a 5-to 7-fold increase in dermal microvascular EC surface protein expression of two collagen receptors-the ␣ 1 ␤ 1 and ␣ 2 ␤ 1 integrins-through induction of mRNAs encoding the ␣ 1 and ␣ 2 subunits. In contrast, VEGF did not induce increased expression of the ␣ 3 ␤ 1 integrin, which also has been implicated in collagen binding. Integrin ␣ 1 -blocking and ␣ 2 -blocking antibodies (Ab) each partially inhibited attachment of microvascular EC to collagen I, and ␣ 1 -blocking Ab also inhibited attachment to collagen IV and laminin-1. Induction of ␣ 1 ␤ 1 and ␣ 2 ␤ 1 expression by VEGF promoted cell spreading on collagen I gels which was abolished by a combination of ␣ 1 -blocking and ␣ 2 -blocking Abs. In vivo, a combination of ␣ 1 -blocking and ␣ 2 -blocking Abs markedly inhibited VEGF-driven angiogenesis; average cross-sectional area of individual new blood vessels was reduced 90% and average total new vascular area was reduced 82% without detectable effects on the pre-existing vasculature. These data indicate that induction of ␣ 1 ␤ 1 and ␣ 2 ␤ 1 expression by EC is an important mechanism by which VEGF promotes angiogenesis and that ␣ 1 ␤ 1 and ␣ 2 ␤ 1 antagonists may prove effective in inhibiting VEGF-driven angiogenesis in cancers and other important pathologies.

show abstract

“…Cell Culture-Human dermal endothelial cells (HDECs) and human endometrial endothelial cells were isolated as described previously (24,25). Mouse brain endothelial cells were harvested from adult mice by enzymatic dissociation and further purified using anti-PECAM (Pharmingen, San Diego, CA) linked to magnetic beads (Dynal, Lake Succes, NY).…”

Section: Methodsmentioning

confidence: 99%

Progesterone Regulates Proliferation of Endothelial Cells

Vázquez

Rodrı́guez-Manzaneque

Lydon

et al. 1999

Journal of Biological Chemistry

124

View full text Add to dashboard Cite

The use of steroid hormones in postmenopausal replacement therapy has been associated with prevention of cardiovascular disease. Although the contribution of estradiol to endothelial cell function has been addressed, little information is available on the effect of progestins on this cell type. Here, we provide direct evidence for the presence of functional nuclear progesterone receptor in endothelial cells and demonstrate that physiological levels of progesterone inhibit proliferation through a nuclear receptor-mediated mechanism. The effects of progesterone were blocked by pretreatment with a progesterone receptor antagonist, and progesterone receptor-deficient endothelial cells failed to respond to the hormone. We evaluated the effect of progesterone by analysis of aorta re-endothelialization experiments in wild-type and progesterone receptor knockout mice. The rate of re-endothelialization was significantly decreased in wild-type mice when in the presence of progesterone, whereas there was no difference between control and progesterone-treated progesterone receptor knockout mice. FACS analysis showed that progestins arrest endothelial cell cycle in G 1 . The lag in cell cycle progression involved reduction in cyclindependent kinase activity, as shown by down-regulation in retinoblastoma protein phosphorylation. In addition, treatment of endothelial cells with progestins altered the expression of cyclin E and A in accordance with G 1 arrest. These results have important implications to our current knowledge of the effect of steroids on endothelial cell function and to the overall contribution of progesterone to vascular repair.

show abstract

Effect of Recombinant Tumor Necrosis Factor-Alpha on Cultured Microvascular Endothelial Cells Derived From Human Dermis

Cited by 38 publications

References 24 publications

Blood and lymphatic endothelial cell-specific differentiation programs are stringently controlled by the tissue environment

Blood and lymphatic endothelial cell-specific differentiation programs are stringently controlled by the tissue environment

Angiogenesis promoted by vascular endothelial growth factor: Regulation through α₁β₁and α₂β₁integrins

Progesterone Regulates Proliferation of Endothelial Cells

Contact Info

Product

Resources

About

Effect of Recombinant Tumor Necrosis Factor-Alpha on Cultured Microvascular Endothelial Cells Derived From Human Dermis

Cited by 38 publications

References 24 publications

Blood and lymphatic endothelial cell-specific differentiation programs are stringently controlled by the tissue environment

Blood and lymphatic endothelial cell-specific differentiation programs are stringently controlled by the tissue environment

Angiogenesis promoted by vascular endothelial growth factor: Regulation through α1β1and α2β1 integrins

Progesterone Regulates Proliferation of Endothelial Cells

Contact Info

Product

Resources

About

Angiogenesis promoted by vascular endothelial growth factor: Regulation through α₁β₁and α₂β₁integrins