Comparative Analysis of the Reactivity of Human Umbilical Vein Endothelial Cells in Organ and Monolayer Culture

Cronen

The Journal of Pathology

et al. 2002

Self Cite

ARDS (acute respiratory distress syndrome) can be associated with septic shock and multiple organ failure caused by an uncontrolled systemic inflammatory response to Gram-negative bacterial infection. While in animal models the key role of the endothelial adhesion molecules ICAM-1, E-selectin, and VCAM in ARDS has been extensively studied, there are scarcely any corresponding pathomorphological studies of human lung tissue. Hence, little is known about whether there is a comparable, or even heterogeneous, expression pattern of these molecules in the human pulmonary vasculature. This study was therefore undertaken to investigate the immunohistochemical expression of the constitutively expressed PECAM (CD31) and the inducible molecules ICAM-1, E-selectin, and VCAM in ARDS lungs from patients who had died in septic shock induced by Gram-negative bacteria. While in all specimens (ARDS and normal lungs) there was homogeneous strong expression of PECAM in all vessels, ICAM-1 was clearly up-regulated in ARDS lungs. E-selectin and VCAM were not expressed by endothelial cells (ECs) in normal lungs, but in ARDS lungs there was strong expression of both molecules in larger vessels, while in the capillaries there was only mosaic-like weak expression of a few ECs. This immunohistochemical investigation demonstrates the induction and up-regulation of adhesion molecules in human ARDS lungs, comparable to that described in animal models. There is also markedly heterogeneous expression of E-selectin and VCAM, indicating toporegional differences in the function of pulmonary ECs.

Section: Discussionsupporting

confidence: 90%

Heterogeneous expression of cell adhesion molecules by endothelial cells in ARDS

Cronen

The Journal of Pathology

et al. 2002

Self Cite

“…Rat anti-human CD31 Ab (1:25 dilution; BD Biosciences PharMingen, San Diego, CA, USA), followed by biotinylated goat anti-rat Ab (1:100 dilution; Jackson ImmunoReseach Laboratories Inc., West Grove, PA, USA) and streptavidin-conjugated horseradish peroxidase (HRP) (DAKO Corp., Carpinteria, California, USA) were used in a protocol previously described. 11 Samples without primary antibody staining served as negative controls.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Hypoxia-induced apoptosis in endothelial cells and embryonic stem cells

et al. 2005

“…This model is much used because of its ready availability but raises the question of its relevance to the situation in the adult human organism. We have performed comparative studies on HUVECs and endothelial cells (ECs) in situ within the umbilical cord in organ culture to compare the gene expression of a variety of endothelial markers, including CAMs, tissue plasminogen activator (tPA), plasminogen activator inhibitor‐1 (PAI‐1), and endothelial nitric oxide synthase (eNOS), both in the unstimulated (basal) state and under the influence of pro‐inflammatory stimuli76. Although differences in expression were found for a few parameters, there was generally a good correlation between both experimental situations.…”

Section: Evidence From In Vitro Studies With Relevance To Microcirculmentioning

confidence: 99%

Microcirculatory dysfunction in sepsis: a pathogenetic basis for therapy?

2000

Sepsis is a frequent complication of multiple organ dysfunction syndrome and remains a major problem of intensive care medicine. It is also a common factor in the final cause of death in hospital populations. Clinical observations, assisted by invasive monitoring techniques as well as pathological–anatomical studies, clearly indicate that microcirculatory dysfunction lies at the centre of sepsis pathogenesis. Numerous animal models, from rodents to primates, many of which employ bacteria or their toxins, especially endotoxins, have helped to shed light on the pathomechanisms leading to this dysregulation in the peripheral circulation. Among these are activation of humoral and cellular inflammatory mediator systems, with special emphasis on neutrophil–endothelial interactions, affecting endothelial barrier function and vasoregulation and ultimately leading to severely perturbed oxygen transport and utilization. In vitro studies have provided more insight into the molecular mechanisms involved in this microcirculatory dysfunction, although much more attention must be directed towards microvascular endothelial cells and the role of heterogeneity of response in various vascular beds. These experimental data must in turn be validated by comparing with the human in situ situation, both clinical and morphological. This review aims at a critical appraisal of the clinical and experimental evidence for sepsis‐induced dysregulation of the microcirculation and how knowledge of the underlying cellular and molecular pathology could be used to make therapy more rational and effective. To date, therapeutic approaches, such as anti‐cytokine and anti‐oxidant regimens, which have been highly successful in experimental models, have failed to demonstrate clinical efficacy. Newer approaches, such as targeting the coagulation system, nitric oxide synthesis or intracellular signal transduction, are also discussed. The necessity to focus on the role of anti‐inflammatory mediators, as well as the pathogenetic significance of important molecular groups, such as the heat shock proteins, which until now have been given scant attention, will be stressed. Copyright © 2000 John Wiley & Sons, Ltd.