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Mast Cell Activation and Leukocyte Rolling Responses
Published in Bruce S. Bochner, Adhesion Molecules in Allergic Disease, 2020
In a human/SCID mouse chimeric model, Christofidou-Solomidou et al. (66) illustrated that a monoclonal antibody against human E-selectin significantly reduced mast cell degranulation-induced leukocyte recruitment at 4 hours. Although the contribution of P-selectin in this model was not determined, an important role for E-selectin in leukocyte recruitment is proposed. On the other hand, mutant mice lacking E-selectin had no leukocytic impairment in delayed-type hypersensitivity responses; however addition of a P-selectin antibody significantly reduced neutrophil infiltrate in this model (67). It should be noted that leukocyte recruitment and the role of TNF-α and E-selectin or any of the other selectins has not been examined in late phase reactions using intravital video microscopy, in part because of the difficulties with maintaining viable preparations for prolonged periods of time. However, we have recently developed a model of late phase reaction that has permitted us to visualize leukocyte recruitment in the cremaster muscle, 8 hours after the intrascrotal administration of ovalbumin in sensitized animals (68). This experiment revealed that a very significant proportion of the leukocyte rolling could be inhibited by a P-selectin antibody. Moreover, no cells could be seen rolling 8 hours after challenge in P-selectin knockout mice, suggesting an unlikely role for E-selectin in the cremaster muscle microcirculation (unpublished observations). Therefore, the importance of E-selectin in the recruitment of rolling leukocytes remains unclear.
Leukocyte/Endothelial Cell Adhesion and Ischemia/Reperfusion Injury
Published in John H. Barker, Gary L. Anderson, Michael D. Menger, Clinically Applied Microcirculation Research, 2019
Gary D. Dunn, D. Neil Granger, Ronald J. Korthuis
The contributions of endothelial E-selectin and leukocyte L-selectin in the pathogenesis of postischemic cellular dysfunction have not been evaluated. However, a role for E-selectin in the recruitment of leukocytes during early reperfusion seems unlikely since the molecule is not normally present on the endothelial cell surface and requires 4–8 h to achieve full expression after exposure to proinflammatory mediators such as interleukin-1 or bacterial lipopolysaccharide.83,84 It is possible that the formation of cytokines during early reperfusion upregulates the expression of E-selectin, which then contributes to the development of more delayed adherence reactions induced by I/R. Furthermore, since skin and skeletal muscle are very resistant to the short periods of ischemia that are so devastating to other organs such as the heart and brain, the duration of ischemia required to produce injury in the extremities (>4 h) may allow for changes that ultimately promote E-selectin expression during reperfusion. Indeed, a preliminary report indicates that E-selectin antibodies reduce microvascular dysfunction in a mouse dorsal skin fold model that involves exposure of the tissue to 4 h of ischemia.85
Endotoxemia in Primate Models
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Heinz Redl, Günther Schlag, Soheyl Bahrami
Endotoxin causes endothelial activation with induction of cytokine production, procoagulatory as well as vasopressor/vasodilator responses, and an increase in adhesion for leukocytes. Cell adhesion molecules, which are responsible for the adhesion and later for the migration of leukocytes into the perivascular space, play a critical role in the development of many inflammatory conditions. One interesting molecule is E-selectin. E-selectin is an endothelial cell-specific adhesion molecule that appears to only be expressed in response to inflammatory stimuli (85). In vivo, E-selectin induction has been seen after local injection of TNF-α in baboon skin (86) and after infusion of live E. coli in baboons (87) as well as endotoxin infusion in cynomolgus monkey (88). Using skin biopsies it was possible to establish a kinetic expression pattern; expression was not prominent at 4–6 hours and not detectable after 10–24 hours, while serum levels of soluble E-selectin were maximal after 24 hours of endotoxic shock conditions. While E-selectin can therefore serve as a marker for endothelial activation, it cannot be determined directly in vivo except by invasive biopsy techniques. Alternatively, the serum level of the soluble form (sE-selectin) can be determined. sE-selectin was released in vivo after application of endotoxin (1.5 mg/kg) in baboons and reached a peak level after 24 hours (58). In baboons with hemorrhagic shock much lower levels (about one third) of sE-selectin were found. Lower sE-selectin indicates a lower endothelial activation after experimental hemorrhagic traumatic shock (with endotoxin translocation from the gut) as compared to endotoxic shock, probably due to much lower endotoxin levels in traumatic shock (58).
Trial watch: an update of clinical advances in photodynamic therapy and its immunoadjuvant properties for cancer treatment
Published in OncoImmunology, 2023
Mafalda Penetra, Luís G. Arnaut, Lígia C. Gomes-da-Silva
Other PDT studies in the clinical setting have been conducted using the methyl derivative of 5-ALA, MAL. In one of these studies from 2012, MAL cream (Metvix®) was applied to BCC patients (n = 8) followed by a LD of 37 J/cm2. Biopsies demonstrated rapid neutrophil infiltration observed as soon as 1 h post-PDT, which significantly increased at 24 h when compared with the baseline of untreated healthy skin. It was also observed that there was an increase on E-selectin, a cell adhesion molecule that is expressed on the surface of endothelial cells. The number of CD4+ and CD8+ T cells were also augmented after PDT but the differences were not statistically significant. This study also revealed that MAL-PDT significantly reduced the number of epidermal Langerhans cells at least until 24 h. The lack of T cells and DC infiltrates may be related to the short time points (24 h) at which these analyses were carried out67. In another study from 2017 using MAL-PDT (3 h MAL occlusion, 37 J/cm2) in ten patients of BCC, tumor biopsies revealed increasing levels of IFN-γ, IL-17, IL-23 and IL-22 at an early time point (0.5 to 2 h after PDT) compared to the baseline (before PDT), which suggest Th1 and Th17 immune responses. This was followed by decreasing levels at 1 week to 3 months after PDT68.
Targeted drug delivery strategy: a bridge to the therapy of diabetic kidney disease
Published in Drug Delivery, 2023
Xian Chen, Wenni Dai, Hao Li, Zhe Yan, Zhiwen Liu, Liyu He
Antibody, a complex protein-based molecule, is a crucial component in the indirect ways of active targeting. Antibodies vary in molecular weight, and those with molecular weight greater than 150 kDa cannot pass through the glomerular filtration barrier. Antibodies with the molecular weight lower than 50 kDa may be promising moieties in the kidney-targeted delivery system as they pass through the glomerular filtration barrier and can be reabsorbed by the proximal tubular cells (Chen et al., 2020a). Bovine albumin-based NPs with the diameters of 10 nm can selectively target the Fc receptor (FcRn) on the surface of podocytes (Wu et al., 2017). Anti-vascular cell adhesion protein 1 (VCAM-1)-rapamycin-SAINT-O-Somes can delivery rapamycin to the kidney and have little effect on cellular viability in order to reduce the side effect (Visweswaran et al., 2015). E-selectin is overexpressed in highly inflammatory renal environments and is also used as an antibody target for NP kidney targeting (Asgeirsdottir et al., 2008).
Association of E-Selectin gene polymorphisms and serum E-Selectin level with risk of coronary artery disease in lur population of Iran
Published in Archives of Physiology and Biochemistry, 2023
Mobin Khoshbin, Seyyed Amir Yasin Ahmadi, Mostafa Cheraghi, Negar Nouryazdan, Mehdi Birjandi, Gholamreza Shahsavari
CAD affects both men and women. The risk factors are common among men and women, however, smoking has more effect on women (Yahagi et al.2015). Aetiology wise, atherosclerosis is an inflammatory process in which reactive oxygen species (ROS) are created by immune cells, endothelium, and smooth muscles. ROS participates in formation of thrombosis as well as affecting lipoproteins. In addition, ROS participates in changing bioavailability of nitric oxide (NO) (Gray et al.2016, Incalza et al.2018, Yalameha 2019). Therefore, CAD and ACS have multifactorial aetiology. From the viewpoint of the inflammatory basis of atherosclerosis, expression of adhesion molecules by endothelial cells results in adhesion and implantation of circulating immune cells especially monocytes in the region of atherosclerosis (Reiss and Glass 2006, Vigetti et al.2010). These adhesion molecules are inter-cellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), E-selectin and P-selectin (Demerath et al.2001). Nowadays the role of circulating levels of such molecules in susceptibility to atherosclerosis are investigated (Eikendal et al.2018). E-selectin results in adhesion of monocytes to endothelium and causes inflammation (Silva et al.2017).