Plasma Endothelin-1, Cytokine, and Prostaglandin E2 Levels in Sickle Cell Disease and Acute Vaso-Occlusive Sickle Crisis

Heme is an important immunostimulating agent and oxidative factor contributing to endothelial cell activation. To investigate the mechanism of heme-induced endothelial cell activation, we analyzed the effect of heme and the inflammatory cytokine, tumor necrosis factor-β (TNF-β), on the expression of the heme-degrading stress protein, heme oxygenase (HO), and adhesion molecules in human umbilical vein endothelial cells (HUVEC). Indirect immunofluorescence double labeling studies demonstrated a simultaneous increase of ICAM-1 and HO-1 after exposure of cells to heme for 24 hr. Co-expression of HO-1 and ICAM-1 was also demonstrated in TNF-β-exposed cells. Dot blot immunoassay and quantitative analysis by ELISA demonstrated that heme treatment for 24 hr caused a 2-fold increase in ICAM-1 expression (P < 0.002) compared with quiescent cells, while in cells stimulated by TNF-β for 24 hr CAM-1 gene expression increased by 5-fold. Moreover, heme exposure also resulted in a marked increase in VCAM-1 and E ...

/pdf/heme-induces-the-expression-of-adhesion-molecules-icam-1-2mimpf5d1y.pdf

Heme induces the expression of adhesion molecules ICAM-1, VCAM-1, and E selectin in vascular endothelial cells.

Previous studies in atopic dermatitis (AD) have shown that acute and chronic skin lesions are associated with a TH2-type profile of cytokine expression. IL-12 and IL-13 are recently described cytokines, which possess TH1-and TH2-like actions, respectively. We have used the technique of in situ hybridization to examine the expression of IL-12 and IL-13 messenger RNA in skin biopsy specimens of acute and chronic skin lesions and uninvolved skin from patients with AD. When compared with normal control skin, the acute and chronic skin lesions and unaffected skin from patients with AD had significantly greater numbers of cells that were positive for IL-13 mRNA (p < 0.05). Acute AD skin lesions expressed a higher number of positive cells than those observed in chronic AD skin lesions (p < 0.05) or psoriasis skin lesions (p < 0.05) There was a significant increase in the numbers of IL-12 mRNA-positive cells in chronic skin lesions compared with acute lesions and uninvolved skin from patients with AD (p < 0.05). These data demonstrate that acute AD skin lesions are associated with an increased expression of IL-13 mRNA. In contrast, the relative increase in IL-12 mRNA in chronic AD skin lesions suggests a possible role for IL-12-producing cells in modulating chronic inflammation.

Iconographies supplémentaires de l'article : In vivo expression of IL-12 and IL-13 in atopic dermatitis

Vascular occlusion is the main cause of the morbidity and mortality observed in patients with sickle cell disease (SCD). Increasing evidence indicates that (activated) neutrophils could play an important role in the initiation and propagation of vaso-occlusive processes in SCD. In this study, the activation state of neutrophils in sickle cell patients was analyzed by determining the level of expression of neutrophil antigens such as CD62L, CD11b, CD66b, CD63, and Fcgamma receptors. We also analyzed plasma levels of lactoferrin, elastase, soluble (s)CD16 (sFcgammaRIII), and serum levels of soluble (s)CD62L (sL-selectin) as neutrophil activation markers in these patients. Significant differences were observed in the activation state of neutrophils in non-symptomatic sickle cell patients compared to healthy HbAA controls as exemplified by significant decrease in L-selectin expression, enhanced expression of CD64, and increased levels of soluble markers like sL-selectin, elastase, and sCD16. During vaso-occlusive crisis the differences were even more pronounced. These results show neutrophils to be activated in sickle cell patients, suggesting a role of importance in the pathophysiology of sickle cell disease.

https://jlb.onlinelibrary.wiley.com/doi/pdf/10.1002/jlb.66.3.411

Neutrophil activation in sickle cell disease.

The HLA molecules are membrane-bound transporters that carry peptides from the cytoplasm to the cell surface for surveillance by circulating T lymphocytes. Although low levels of soluble HLA molecules (sHLA) are normally released into the blood, many types of tumor cells release larger amounts of these sHLA molecules, presumably to counter immune surveillance by T cells. Here we demonstrate that these sHLA molecules are still bound with their authentic peptide repertoires, similar to those of the membranal HLA molecules (mHLA). Therefore, a single immunoaffinity purification of the plasma sHLA molecules, starting with a few milliliters of patients' blood, allows for identification of very large sHLA peptidomes by mass spectrometry, forming a foundation for development of a simple and universal blood-based cancer diagnosis. The new methodology was validated using plasma and tumor cells of multiple-myeloma and leukemia patients, plasma of healthy controls, and with cultured cancer cells. The analyses identified thousands of sHLA peptides, including some cancer-related peptides, present among the sHLA peptidomes of the cancer patients. Furthermore, because the HLA peptides are the degradation products of the cellular proteins, this sHLA peptidomics approach opens the way for investigation of the patterns of protein synthesis and degradation within the tumor cells.

https://www.pnas.org/content/pnas/107/44/18769.full.pdf

Soluble plasma HLA peptidome as a potential source for cancer biomarkers

Objective: Our objective is to review the role of adhesion molecules, cytokines, and inflammation in the abnormal adherence of sickle red blood cells to vascular endothelia in the pathogenesis of vascular complication in patients with sickle cell anemia. Data Sources: The MEDLINE database was used to review the hematologic, immunologic, and allergy literature in English with respect to the adhesion molecules involved in sickle hematopoiesis and vascular complications. Study Selection: Studies selected for review were those that identified the adhesion molecules involved in reticulocyte-endothelial adhesion and the influence that cytokines, infections, and atopy have upon the expression of these molecules. Results: In sickle cell disease, a constant low level of inflammation caused by abnormal adhesion of sickle erythrocytes to endothelial cells in the microvasculature produces low-level tissue ischemia. Allergic and infectious inflammations are likely to lead to increased sickle erythrocyte trapping in the microvascular endothelia which progresses to vessel obstruction, end organ ischemic damage, and dysfunction. Conclusion: The identification of underlying immune defects that predispose patients to infections and inflammation needs to be emphasized. Anti-inflammatory medications, anti-adhesion molecule monoclonal antibodies, and adhesion molecule binding-site analogs may have a future in the treatment of the acute vascular complications of sickle cell disease. Ann Allergy Asthma Immunol 1996;76:385–403.

New concepts in the immunology of sickle cell

Background Atopic dermatitis is characterized by increased production of IgE and interleukin-4, immediate skin test reactivity to allergens, increased expression of CD23 on mononuclear cells, and decreased production of interferon-gamma Soluble HLA-I molecule levels are elevated in conditions where T cells are activated such as viral infections, autoimmune diseases, and organ transplantation Objective We wished to determine if sHLA-heterodimers were also elevated in patients with atopic dermatitis and if sHLA-I elevations correlated with disease activity Methods Fourteen children with atopic dermatitis resistant to conventional treatment were followed over an 8-week period during an ongoing trial of treatment with topical sodium cromoglycate Extent of skin involvement, disease severity, absolute eosinophil counts, IgE and HLA-I levels were determined at the time of enrollment into the study Additional sHLA-I levels were measured after 4 and 8 weeks of therapy Results Mean sHLA-I levels were significantly elevated in atopic dermatitis patients, 207 ± 114 versus 100 ± 022 micrograms/mL in controls (P 0001) Nine of 14 patients (64%) had elevated sHLA-I antigens Soluble HLA-I levels did not correlate with the extent of disease, disease severity score, eosinophil count, or IgE levels There was a remarkable consistency in sHLA-I levels at baseline and after 4 and 8 weeks of therapy, even with significant clinical improvement Conclusion We conclude that sHLA-I heterodimers are elevated in 64% of our patients with atopic dermatitis and that elevations persist after clinically effective therapy This conclusion supports recommendations for prolonged preventative and treatment measures in this atopic disease

Elevated Levels of Soluble HLA Class I (sHLA-1) in Children with Severe Atopic Dermatitis

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Mohammad Ehlayel

Author Tools

Chat about Author

Papers

New concepts in the immunology of sickle cell

Elevated Levels of Soluble HLA Class I (sHLA-1) in Children with Severe Atopic Dermatitis