Neutrophils adhesion to endothelial cells

Carveth, H.J., Shaddy, R.E., Whatley, R.E., McIntyre, T.M., Preseott, S.M. and Zimmerman, G.A. (1992). Regulation of platelet-activating factor (PAF) synthesis and PAF-mediated neutrophil adhesion to endothelial cells activated by thrombin. Semin. Thromb. Hemost. 18, 126-134. 

An essential step in phagocytosis involves travel of neutrophils to the site of infection through their adherence to the vessel wall and travel between endothelial cells (diapedesis). Jonas et al (1993) reported that ascorbate reduced neutrophil adhesion to endothelial cells and provided a protective effect this conclusion was not valid because the difference between ascorbate-treated and control groups was only 1%. In another report, on seven patients who had renal transplant (Thomer et al., 1983), ascorbate was shown to increase neutrophil adhesion. More studies with larger sample size are needed to elucidate further the role of ascorbate in adhesion. 

PF4. CXCL4. Belongs to inflammatory cytokines family, mediates the relationship between monocytes and endothelial cells, induces neutrophil adhesion and secondary granule exocytosis, and influences macrophages adhesion to endothelial cell by triggering monocyte arrest in atherosclerotic arteries... 

In vitro studies have documented that activation of leukocytes by ANCAs can release factors that are injurious to endothelial cells (52-59). Endothelial injury by ANCA-activated leukocytes requires interplay between multiple cytokine and adhesion molecule ligands and their receptors in the microenvironment at the site of vasculitis (55-59). Overall, in vitro activation of neutrophils by ANCA IgG causes neutrophil adherence to endothelial cells, diapedesis through endothelial monolayers, and release of toxic factors that kill endothelial cells (Fig. 1). Similar events in vivo would result in histologic changes that are characteristic of early acute ANCA-associated vasculitis, including neutrophil margination and infiltration and vascular necrosis. 

Figure 2. (1) Neutrophils circulating passively in blood capillary. (2) Chemoattractants may be detected by the circulating neutrophils, by the endothelial cells lining the lumen, or both in order that the neutrophils become adhesive. This adhesion is mediated by selectins, a group of cell surface proteins. Neutrophils roll on the surface of the endothelial cells and then actively locomote seeking out spaces between the endothelial cells. (3) The adhesive neutrophils begin to squeeze between endothelial cells. (4) Cells move through the extracellular matrix towards the site of infection. Here adhesion is low and may not be necessary for locomotion. (5) At the site of infection, neutrophils become trapped by increased adhesion where they phagocytose bacteria and liberate the contents of their granules. After Lackie (1982,1986).

Integrins Mediate Adhesion of Neutrophils to Endothelial Cells... 

Adhesion of neutrophils to endothelial cells employs specific adhesive proteins (integrins) located on their surface and also specific receptor proteins in the endothelial cells. (See also the discussion of selectins in Chapter 47.)... 

Schaefer U, Schneider A, Rixen D, Neugebauer E (1998) Neutrophil adhesion to histamine stimulated cultured endothelial cells is primarily mediated via activation of phospholipase C and nitric oxide synthase isozymes. Inflamm Res 47(6) 256-264 Schaefer U, Schmitz V, Schneider A, Neugebauer E (1999) Histamine induced homologous and heterologous regulation of histamine receptor subtype mRNA expression in cultured endothelial ceUs. Shock 12(4) 309-315... 

To clarify the inhibitory effects of these flavonoids from Scutellariae radix on adjuvant-induced arthritis, we further examined the effects of these flavonoids on leukotriene synthesis and adhesion molecular expression in neutrophils and vein endothelial cells. Baicalein inhibited the biosynthesis of LTs B4 and C4 in human leukocytes most strongly... 

There is no cure for sickle cell disease and current therapies are aimed at managing the nnmerons complications associated with the condition. These therapies inclnde penicillin treatment, iimnunization against Streptococcus pneumoniae, blood transfusions, and hydroxyurea (12,20). Hydroxyurea is the only drug therapy specific for sickle cell disease. Hydroxyurea appears to act through several mechanisms, including increased production of fetal hemoglobin, reduced adhesion of blood cells to endothelial cells, improved erythrocyte hydration, and reduced neutrophil counts (21). Hydroxyurea has proven effective but there are some concerns with toxicity and not all patients respond to the treatment (21-23). There is clearly a need for development of additional therapies. 

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