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.

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.

Sickle Cell Disease and the Eye: Old and New Concepts

The pathogenesis of sickle vaso-occlusive crisis (VOC) in sickle cell disease (SCD) patients involves the accumulation of rigid sickle cells and the stimulation of an ongoing inflammatory response, as well as the stress of infections. The immune response, via cytokine imbalances and deregulated T-cell subsets, also has been proposed to contribute to the development of VOC. In this study, a panel of high-sensitivity cytokine kits was used to investigate cytokines in the sera of SCD patients in VOC. The results were compared primarily with those for stable SCD patients and secondarily with those for normal healthy people who served as controls. The cytokines studied included interleukin-2 (IL-2), IL-4, and IL-10. Lymphocyte subsets of patients with VOC were also studied and were compared with those of both control groups (20 stable patients without crisis [SCD group] and 20 normal healthy controls [NHC]). The VOC group was notable for remarkably elevated levels of IL-4, among the three cytokines tested, compared with those for the SCD and NHC groups. Patients with VOC also differed from stable SCD patients and NHC by having notably lower IL-10 levels, as well as the lowest ratio of CD4(+) to CD8(+) T cells (0.7). The patterns of the proinflammatory cytokine IL-2 did not differ between VOC and stable SCD patients, but NHC had significantly lower IL-2 levels than both the VOC and SCD groups. Our results demonstrate coexisting levels, both high and low, of TH1- and TH2-type cytokines, as well as diminished levels of T-cell subsets in VOC. These results are discussed in an effort to better understand the importance of the immune system profile in the pathogenesis of sickle cell VOC. Since the possibility that a cytokine imbalance is implicated in the pathogenesis of sickle cell crisis has been raised, our results should prompt further investigation of the host immune response in terms of TH1 and TH2 balance in sickle cell crisis.

https://cvi.asm.org/content/cdli/17/4/602.full.pdf

Pattern of Serum Cytokine Expression and T-Cell Subsets in Sickle Cell Disease Patients in Vaso-Occlusive Crisis

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

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New concepts in the immunology of sickle cell