scholarly journals Rickettsia rickettsii Infection of Human Macrovascular and Microvascular Endothelial Cells Reveals Activation of Both Common and Cell Type-Specific Host Response Mechanisms

2010 ◽  
Vol 78 (6) ◽  
pp. 2599-2606 ◽  
Author(s):  
Elena Rydkina ◽  
Loel C. Turpin ◽  
Sanjeev K. Sahni
Keyword(s):  
Endothelial Cells ◽  
Host Response ◽  
Cell Types ◽  
Microvascular Endothelial Cells ◽  
Cell Type ◽  
Rickettsia Rickettsii ◽  
Specific Host ◽  
Cell Type Specific ◽  
Cox 2 ◽  
Microvascular Endothelial

ABSTRACT Although inflammation and altered barrier functions of the vasculature, due predominantly to the infection of endothelial cell lining of small and medium-sized blood vessels, represent salient pathological features of human rickettsioses, the interactions between pathogenic rickettsiae and microvascular endothelial cells remain poorly understood. We have investigated the activation of nuclear transcription factor-kappa B (NF-κB) and p38 mitogen-activated protein (MAP) kinase, expression of heme oxygenase 1 (HO-1) and cyclooxygenase 2 (COX-2), and secretion of chemokines and prostaglandins after Rickettsia rickettsii infection of human cerebral, dermal, and pulmonary microvascular endothelial cells in comparison with pulmonary artery cells of macrovascular origin. NF-κB and p38 kinase activation and increased HO-1 mRNA expression were clearly evident in all cell types, along with relatively similar susceptibility to R. rickettsii infection in vitro but considerable variations in the intensities/kinetics of the aforementioned host responses. As expected, the overall activation profiles of macrovascular endothelial cells derived from human pulmonary artery and umbilical vein were nearly identical. Interestingly, cerebral endothelial cells displayed a marked refractoriness in chemokine production and secretion, while all other cell types secreted various levels of interleukin-8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) in response to infection. A unique feature of all microvascular endothelial cells was the lack of induced COX-2 expression and resultant inability to secrete prostaglandin E2 after R. rickettsii infection. Comparative evaluation thus yields the first experimental evidence for the activation of both common and unique cell type-specific host response mechanisms in macrovascular and microvascular endothelial cells infected with R. rickettsii, a prototypical species known to cause Rocky Mountain spotted fever in humans.

scholarly journals Cell type-specific biogenesis of novel vesicles containing viral products in human cytomegalovirus infection

2020 ◽  
Author(s):  
Samina Momtaz ◽  
Belen Molina ◽  
Luwanika Mlera ◽  
Felicia Goodrum ◽  
Jean M. Wilson
Keyword(s):  
Endothelial Cells ◽  
Human Cytomegalovirus ◽  
Biosynthetic Pathway ◽  
Cell Types ◽  
Endocytic Pathway ◽  
Specific Cell ◽  
Cell Type ◽  
Subcellular Compartment ◽  
Increased Risk ◽  
Cell Type Specific

AbstractHuman cytomegalovirus (HCMV), while highly restricted for the human species, infects an unlimited array of cell types in the host. Patterns of infection are dictated by the cell type infected, but cell type-specific factors and how they impact tropism for specific cell types is poorly understood. Previous studies in primary endothelial cells showed that HCMV infection induces large multivesicular-like bodies that incorporate viral products including dense bodies and virions. Here we define the nature of these large vesicles using a recombinant virus where UL32, encoding the pp150 tegument protein, is fused in frame with green fluorescent protein (GFP, TB40/E-UL32-GFP). Cells were fixed and labeled with antibodies against subcellular compartment markers and imaged using confocal and super-resolution microscopy. In fibroblasts, UL32-GFP-positive vesicles were marked with classical markers of MVBs, including CD63 and lysobisphosphatidic acid (LBPA), both classical MVB markers, as well as the clathrin and LAMP1. Unexpectedly, UL32-GFP-positive vesicles in endothelial cells were not labeled by CD63, and LBPA was completely lost from infected cells. We defined these UL32-positive vesicles in endothelial cells using markers for the cis-Golgi (GM130), lysosome (LAMP1), and autophagy (LC3B). These findings suggest that virus-containing MVBs in fibroblasts are derived from the canonical endocytic pathway and takeover classical exosomal release pathway. Virus containing MVBs in HMVECs are derived from the early biosynthetic pathway and exploit a less characterized early Golgi-LAMP1-associated non-canonical secretory autophagy pathway. These results reveal striking cell-type specific membrane trafficking differences in host pathways that are exploited by HCMV.ImportanceHuman cytomegalovirus (HCMV) is a herpesvirus that, like all herpesvirus, that establishes a life long infection. HCMV remains a significant cause of morbidity and mortality in the immunocompromised and HCMV seropositivity is associated with increased risk vascular disease. HCMV infects many cells in the human and the biology underlying the different patterns of infection in different cell types is poorly understood. Endothelial cells are important target of infection that contribute to hematogenous spread of the virus to tissues. Here we define striking differences in the biogenesis of large vesicles that incorporate virions in fibroblasts and endothelial cells. In fibroblasts, HCMV is incorporated into canonical MVBs derived from an endocytic pathway, whereas HCMV matures through vesicles derived from the biosynthetic pathway in endothelial cells. This work defines basic biological differences between these cell types that may impact the outcome of infection.

scholarly journals COX-1 and COX-2 Contributions to Basal and IL-1β-Stimulated Prostanoid Synthesis in Human Neonatal Cerebral Microvascular Endothelial Cells

2002 ◽  
Vol 52 (3) ◽  
pp. 342-348 ◽  
Author(s):  
Helena Parfenova ◽  
Vladimir Levine ◽  
Wendy M Gunther ◽  
Massroor Pourcyrous ◽  
Charles W Leffler
Keyword(s):  
Endothelial Cells ◽  
Microvascular Endothelial Cells ◽  
Cox 2 ◽  
Microvascular Endothelial ◽  
Cox 1 ◽  
Prostanoid Synthesis

scholarly journals Sodium butyrate inhibits angiogenesis of human intestinal microvascular endothelial cells through COX-2 inhibition

FEBS Letters ◽  
2003 ◽  
Vol 554 (1-2) ◽  
pp. 88-94 ◽  
Author(s):  
Hitoshi Ogawa ◽  
Parvaneh Rafiee ◽  
Pamela J. Fisher ◽  
Nathan A. Johnson ◽  
Mary F. Otterson ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Sodium Butyrate ◽  
Microvascular Endothelial Cells ◽  
Cox 2 ◽  
Microvascular Endothelial

Nucleoside and nucleobase transporters of primary human cardiac microvascular endothelial cells: characterization of a novel nucleobase transporter

2007 ◽  
Vol 293 (6) ◽  
pp. H3325-H3332 ◽  
Author(s):  
Derek B. J. Bone ◽  
James R. Hammond
Keyword(s):  
Endothelial Cells ◽  
Cell Types ◽  
Microvascular Endothelial Cells ◽  
Nucleoside Transporter ◽  
Active Metabolites ◽  
Equilibrative Nucleoside Transporter ◽  
Microvascular Endothelial ◽  
Cardiac Microvascular Endothelial Cells ◽  
Nucleobase Transport

Levels of cardiovascular active metabolites, like adenosine, are regulated by nucleoside transporters of endothelial cells. We characterized the nucleoside and nucleobase transport capabilities of primary human cardiac microvascular endothelial cells (hMVECs). hMVECs accumulated 2-[3H]chloroadenosine via the nitrobenzylmercaptopurine riboside-sensitive equilibrative nucleoside transporter 1 (ENT1) at a Vmaxof 3.4 ± 1 pmol·μl−1·s−1, with no contribution from the nitrobenzylmercaptopurine riboside-insensitive ENT2. Inhibition of 2-chloroadenosine uptake by ENT1 blockers produced monophasic inhibition curves, which are also compatible with minimal ENT2 expression. The nucleobase [3H]hypoxanthine was accumulated within hMVECs ( Km= 96 ± 37 μM; Vmax= 1.6 ± 0.3 pmol·μl−1·s−1) despite the lack of a known nucleobase transport system. This novel transporter was dipyridamole-insensitive but could be inhibited by adenine ( Ki= 19 ± 7 μM) and other purine nucleobases, including chemotherapeutic analogs. A variety of other cell types also expressed the nucleobase transporter, including the nucleoside transporter-deficient PK( 15 ) cell line (PK15NTD). Further characterization of [3H]hypoxanthine uptake in the PK15NTD cells showed no dependence on Na+or H+. PK15NTD cells expressing human ENT2 accumulated 4.5-fold more [3H]hypoxanthine in the presence of the ENT2 inhibitor dipyridamole than did PK15NTD cells or hMVECs, suggesting trapping of ENT2-permeable metabolites. Understanding the nucleoside and nucleobase transporter profiles in the vasculature will allow for further study into their roles in pathophysiological conditions such as hypoxia or ischemia.

scholarly journals Up-regulation of COX-2/PGE2 by endothelin-1 via MAPK-dependent NF-κB pathway in mouse brain microvascular endothelial cells

2013 ◽  
Vol 11 (1) ◽  
pp. 8 ◽  
Author(s):  
Chih-Chung Lin ◽  
Hsi-Lung Hsieh ◽  
Ruey-Horng Shih ◽  
Pei-Ling Chi ◽  
Shin-Ei Cheng ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mouse Brain ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Endothelin 1 ◽  
Cox 2 ◽  
Microvascular Endothelial

Upregulation of COX-2/PGE2 by ET-1 Mediated Through Ca2+-Dependent Signals in Mouse Brain Microvascular Endothelial Cells

2013 ◽  
Vol 49 (3) ◽  
pp. 1256-1269 ◽  
Author(s):  
Chih-Chung Lin ◽  
Hsi-Lung Hsieh ◽  
Pei-Ling Chi ◽  
Chien-Chung Yang ◽  
Li-Der Hsiao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mouse Brain ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Cox 2 ◽  
Microvascular Endothelial

scholarly journals Profiling of Primary and Mature miRNA Expression in Atherosclerosis Associated Cell Types

2021 ◽  
Author(s):  
Pierre R. Moreau ◽  
Vanesa Tomas Bosch ◽  
Maria Bouvy-Liivrand ◽  
Kadri Õunap ◽  
Tiit Örd ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Cell Types ◽  
Integrative Approach ◽  
Dependent Manner ◽  
Cell Type ◽  
A Cell ◽  
Cell Type Specific

Objective: Atherosclerosis is the underlying cause of most cardiovascular diseases. The main cell types associated with disease progression in the vascular wall are endothelial cells, smooth muscle cells, and macrophages. Although their role in atherogenesis has been extensively described, molecular mechanisms underlying gene expression changes remain unknown. The objective of this study was to characterize microRNA (miRNA)-related regulatory mechanisms taking place in the aorta during atherosclerosis: Approach and Results: We analyzed the changes in primary human aortic endothelial cells and human umbilical vein endothelial cell, human aortic smooth muscle cell, and macrophages (CD14+) under various proatherogenic stimuli by integrating GRO-seq, miRNA-seq, and RNA-seq data. Despite the highly cell-type-specific expression of multi-variant pri-miRNAs, the majority of mature miRNAs were found to be common to all cell types and dominated by 2 to 5 abundant miRNA species. We demonstrate that transcription contributes significantly to the mature miRNA levels although this is dependent on miRNA stability. An analysis of miRNA effects in relation to target mRNA pools highlighted pathways and targets through which miRNAs could affect atherogenesis in a cell-type-dependent manner. Finally, we validate miR-100-5p as a cell-type specific regulator of inflammatory and HIPPO-YAP/TAZ-pathways. Conclusions: This integrative approach allowed us to characterize miRNA dynamics in response to a proatherogenic stimulus and identify potential mechanisms by which miRNAs affect atherogenesis in a cell-type-specific manner.

Clot Lysis Mediated by Cultured Human Microvascular Endothelial Cells

1988 ◽  
Vol 60 (03) ◽  
pp. 463-467 ◽  
Author(s):  
Wolfgang Speiser ◽  
Elisabeth Anders ◽  
Bernd R Binder ◽  
Gert Müller-Berghaus
Keyword(s):  
Endothelial Cells ◽  
Plasminogen Activator ◽  
Shape Change ◽  
Umbilical Vein ◽  
Cell Types ◽  
Microvascular Endothelial Cells ◽  
Clot Lysis ◽  
Microvascular Endothelial ◽  
Umbilical Vein Endothelial Cells ◽  
Fibrin Clots

SummaryThe lysis of fibrin clots on the surface of cultured human omental tissue microvascular endothelial cells (HOTMEC) and cultured human umbilical vein endothelial cells (HUVEC) was studied. Fibrin clots were made by mixing fibrinogen, plasminogen and thrombin on the surface of both cell types. Clot lysis was seen only on the surface of HOTMEC, which were found to synthesize about 100-fold more tissue plasminogen activator (tPA) antigen than HUVEC. Clot lysis of HOTMEC could be blocked by anti-tPA IgG but was not affected by the incorporation of exogenous plasminogen activator (PAI) into the clot in concentrations (75 arbitrary units) exceeding the tPA activity (21 ± 2.5 IU) of the cells. Thus, it is likely that tPA secreted by HOTMEC is protected from inhibition by PAI in the presence of fibrin and endothelial cells. The stimulation of EC to release an excess of tPA over PAI, in contrast to the secretion of an excess of PAI over tPA found in unstimulated cells in the absence of fibrin, is obviously no prerequisite for the initiation of fibrinolysis on the surface of HOTMEC. As thrombin was used for clot formation, its influence on tPA and PAI synthesis of both cell types was investigated. In contrast to HOTMEC, which were not affected by Α-thrombin, HUVEC revealed a dose-dependent increase in tPA and PAI synthesis upon incubation with the enzyme. This increase in tPA production by HUVEC was not sufficient to lyse the clots within 48 hours. Furthermore, HUVEC. behaved differently towards thrombin as these cells in contrast to HOTMEC revealed the typical shape change reaction upon incubation with the enzyme

Tumor cells induce COX-2 and mPGES-1 expression in microvascular endothelial cells mainly by means of IL-1 receptor activation

2011 ◽  
Vol 81 (3) ◽  
pp. 261-268 ◽  
Author(s):  
Kelly Casós ◽  
Laura Siguero ◽  
María-Teresa Fernández-Figueras ◽  
Xavier León ◽  
María-Pilar Sardá ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Cells ◽  
Receptor Activation ◽  
Microvascular Endothelial Cells ◽  
Cox 2 ◽  
Microvascular Endothelial
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