Endothelial In Vitro Models

The endothelium is a unicellular layer which constitutes the interphase between blood and tissue. As such, it forms, like epithelia, a physical barrier between 'inside' and 'outside' and fungi have to cross through it to cause a systemic disease. Located at the luminal side of blood vessels, the endothelium is a dynamic and heterogeneous organ which fulfils vital secretory, synthetic, metabolic, and immunologic functions (Cines et al., 1998; Fishman, 1982). It regulates the flow of the blood itself as well as the exchange of metabolites and various biologically active molecules between both compartments.

Endothelia exert their gate keeping role through the presence of receptors for a variety of molecules (proteins, lipid transporting particles, metabolites, and hormones) as well as through receptors and specific proteins which govern cell-cell and cell-extracellular matrix contacts (Cines et al., 1998). According to their organ-specific function endothelia are characterized by different degrees of permeability which can be relatively pronounced in discontinuous and fenestrated endothelia. In contrast, the continuous endothelium which constitutes the blood-brain barrier (BBB) is highly restrictive to the passage of molecules (Moody, 2006).

Apart from its role as physiological barrier, the endothelium is also a site of interaction with cells of the innate and the adaptive immune system. EC recruit circulating leukocytes to spots of infection where the immune cells gain access to microbes located in the tissue. Leukocytes extravasate from the vessels and initiate the inflammatory process (Ley, 1996; Vestweber, 2002).

Reflecting their various physiological functions, EC exhibit a number of cell type-specific characteristics whose recognition is a prerequisite for the production of primary EC cultures. Von Willebrand factor (vWF) is constitutively expressed in EC from veins and an important marker for cell type identity (Hoyer et al., 1973; Jaffe et al., 1974). Also, almost exclusively expressed on EC are platelet endothelial cell adhesion molecule (PECAM-1, CD31) (Albelda et al., 1990), and vascular endothelial growth factor receptors (Hewett & Murray, 1996; Thomas, 1996). Quiescent EC can be activated in response to pro-inflammatory mediators such as tumour necrosis factor a (TNFa) (Pober et al., 1986); EC respond to these stimuli by surface expression of cell adhesion molecules (e.g. ICAMs, VCAM-1, and E-selectin) (Dustin & Springer, 1988; Bevilacqua, 1993; Osborn et al., 1989). In turn, EC themselves secrete pro-inflammatory cytokines like interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemoattractant protein 1 (MCP-1) (Gimbrone et al., 1989; May et al., 1989; Rollins et al., 1990). The endothelial surface is decorated by a large variety of extracellular domains of membrane-bound molecules, which together constitute the glycocalyx that lines the luminal surface of the endothelium (Pries et al., 2000). Much information has been gathered with respect to specific membrane-bound molecules such as the selectins and integrins (Risau & Flamme, 1995), involved in immune reactions and inflammatory processes (Springer, 1994). Advances in electron microscopy established the concept of a thick surface layer on EC (ESL) at the luminal side, whose consequences for EC function are not yet fully understood (Pries & Kuebler, 2006). All these surface molecules are prone to be exploited by invading pathogens as interactive structures.

Cure Your Yeast Infection For Good

Cure Your Yeast Infection For Good

The term vaginitis is one that is applied to any inflammation or infection of the vagina, and there are many different conditions that are categorized together under this ‘broad’ heading, including bacterial vaginosis, trichomoniasis and non-infectious vaginitis.

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