Infection-driven periodontal disease
Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald in Principles of Mucosal Immunology, 2020
Endothelial cells activated by the cytokines are active participants in the pathogenesis of periodontal inflammation. Secretion of endothelial cell chemokines (CXCL8, CCL2) and expression of adhesion molecules (P- and E-selectin and intercellular adhesion molecule (ICAM)-1 and ICAM-2) on the surface of endothelial cells promote leukocyte extravasation. P- and E-selectins bind glycoproteins on leukocytes and promote rolling of cells along the vessel wall. Firm binding of leukocytes to endothelium is mediated by integrins (leukocyte function-associated antigen-1 [LFA-1]), and leukocytes attach firmly to ICAM-1 expressed on endothelial cells; TNFα, PGE2, and histamine increase vascular permeability and permit leukocyte diapedesis. Chemokines, such as IL-8, that are produced at the site of infection, along with bacterial chemoattractants (the tripeptide fMLP [N-formyl-methionine-leucine-phenylalanine]), form a concentration gradient for leukocytes to migrate to the focus of infection. Circulating pro-inflammatory cytokines from the site of inflammation activate hepatocytes in the liver to release acute-phase proteins, including LPS-binding protein and sCD14 that are important for the recognition of LPS. Complement proteins and C-reactive protein (CRP) are also released to opsonize bacteria for phagocytosis. Figure 29.2 illustrates the initiation sequence of inflammation at the gingiva.
Maturation, Barrier Function, Aging, and Breakdown of the Blood–Brain Barrier
Shamim I. Ahmad in Aging: Exploring a Complex Phenomenon, 2017
While peripheral blood leukocyte infiltration plays an essential role in lesion development, there is also evidence suggesting that BBB dysfunction precedes immune cell infiltration. Recent evidence suggests that immune-mediated activation (or damage) of the various BBB cellular components significantly contributes to lesion development and progression (McQuaid et al. 2009, Alvarez et al. 2011a, b). Chemokines seem to play an important role in the cascade of leukocyte extravasation. Chemokines displayed along the endothelial lumen bind chemokine receptors on circulating leukocytes, initiating intracellular signaling that culminates in integrin activation, leukocyte arrest, and extravasation (Holman et al. 2011).
Ischemia-Reperfusion: A Model of Acute Intestinal Inflammation
William J. Snape, Stephen M. Collins in Effects of Immune Cells and Inflammation on Smooth Muscle and Enteric Nerves, 2020
Until recently the premise that reperfusion promotes the adherence of leukocytes to microvascular endothelium was largely based on tissue myeloperoxidase measurements and observations that monoclonal antibodies directed against leukocyte adhesion molecules protect tissues against reperfusion injury.22–24 However as shown in Table II, the intravital microscopy experiments produce a quantitative assessment of the number of cells that adhere and extravasate under control, ischemic, and reperfusion conditions. Prior to ischemia the number of adherent leukocytes per 100 μm length of mesenteric venules was 4.0 ± 0.8. This value increased to 17.6 ± 0.4 during the last 10 min of a 60 min ischemic period. There was a rapid increase to 28.0 ± 5.4 adherent leukocytes within the first 10 min of reperfusion and this level was maintained for the next 60 min. The fact that neutrophil adherence increased dramatically within the very short initial period of reperfusion (10 min) would suggest that reperfusion or reoxygenation of ischemic mesentery per se increased neutrophil adherence to venular endothelium. Table II also presents the data for leukocyte extravasation prior to, during, and following the ischemic period. There was a progressive rise in the number of leukocytes observed in the interstitium from 8.6 ± 1.5 under control conditions to 29.2 ± 6.0 at the end of the ischemic period, to 68.6 ± 5.6 during 60 min of reperfusion. From these data one can calculate that approximately 21 leukocytes extravasated during the 1 hour of ischemia while 39 leukocytes emigrated during the 1 hr of reperfusion. Thus, the rate of leukocyte extravasation essentially doubled following reperfusion of ischemic tissue. Therefore, both the adherence and extravasation data suggest that a mechanism not present during ischemia is activated during the reperfusion phase.
SOD3 boosts T cell infiltration by normalizing the tumor endothelium and inducing laminin-α4
Published in OncoImmunology, 2020
Lorena Carmona-Rodríguez, Diego Martínez-Rey, Emilia Mira, Santos Mañes
Leukocyte extravasation from the bloodstream into a tissue entails sequential adhesion steps regulated by adhesion receptors and chemokines that culminates in crossing of the endothelial cell (EC) layer. Adhesion receptors, common to all endothelia, are necessary for diapedesis of all leukocyte types. Downmodulation of the main EC adhesion molecules (ICAM-1 or VCAM-1) is a feature of tumors with “immune desertification”. Inflamed tumors can also fine-tune infiltration of effector and suppressor immune cells by modulating chemokine expression.2 To reach the tumor parenchyma, leukocytes must also cross the EC-BM, the main extracellular matrix structure that lies beneath EC.3 EC-BM constituents include type IV collagen, fibronectin, perlecan, nidogen, and laminins. Laminins are particularly interesting, since the laminin-α4 (LAMA4) subunit enhances, whereas laminin-α5 (LAMA5) inhibits T cell diapedesis.3 How the TME influences EC-BM is not known precisely, although it can be predicted that tumor blood vessel abnormalities affect EC-BM composition and integrity.
Assessment of relationship between serum vascular adhesion protein-1 (VAP-1) and gestational diabetes mellitus
Published in Biomarkers, 2019
Burcu Dincgez Cakmak, Betul Dundar, Fatma Ketenci Gencer, Durkadin Elif Yildiz, Feyza Bayram, Gulten Ozgen, Burcu Aydin Boyama
Vascular adhesion protein-1 (VAP-1) is a 170-kDa homodimeric dual-function glycoprotein. It is secreted by endothelial cells, adipocytes, vascular smooth muscle cells, kidney and liver and can act as a surface adhesion molecule (Salmi et al. 1993, Merinen et al. 2005). Moreover, it plays a crucial role in carbohydrate dependent leukocyte adhesion, rolling and transmigration, which are main steps of leukocyte extravasation to the sites of inflammation (Mazzone et al. 2008). VAP-1 has also a copper-containing semicarbazide-sensitive amine oxidase (SSAO) with functional monoamine oxidase activity, which can catalyse primary amine breakdown to produce aldehyde, hydrogen peroxide and ammonia. They are sources of oxidative stress and can contribute to the initiation and progression of inflammatory lesions, DM complications and atherosclerosis (Yu et al. 2003). Increased VAP-1 levels are related with type 2 DM, atherosclerosis, stroke, chronic renal failure and hepatic diseases (Lin et al. 2008, Li et al. 2009, 2011, Hernandez-Guillamon et al. 2012).
Hypoplastic thrombocytopenia and platelet transfusion: therapeutic goals
Published in Hospital Practice, 2019
Stamatis J. Karakatsanis, Stamatis S. Papadatos, Konstantinos N. Syrigos
Corticosteroids, estrogens, desmopressin, recombinant factor VIIa, thrombopoietic growth factors, and intravenous IgG have also been administered for the prevention of bleeding in thrombocytopenic patients [20,42–45], with each one of these drugs having potential side-effects (hypertension, psychological disorders, Cushing’s syndrome, hyperglycemia, and diabetes, weight gain, peptic ulcer, osteoporosis, cataract formation, and glaucoma among others for corticosteroids, vaginal hemorrhage, endometrium disease, edema, hypertension, headache, anxiety, and depression, rash, pruritus, weight gain, hot flashes, and gastrointestinal disorders for estrogens, hyponatremia for desmopressin, thrombosis for recombinant factor VIIa, thrombocytosis, thrombosis, increased bone marrow fibrosis and rebound thrombocytopenia for thrombopoietic growth factors, and headache, thromboembolism, hemolysis, and acute renal failure for intravenous IgG) (Table 3). Moreover, a recent study has recently shown that leukocyte extravasation to the site of tissue inflammation increases the bleeding risk in patients with thrombocytopenia and therefore targeted pharmacological interventions (e.g. pertussis toxin) could be of value for these patients [46]. However, a recent meta-analysis and systematic review that examined whether any alternative agent can prevent bleeding better than prophylactic PLT transfusions found insufficient evidence to support an alternative agent [47]. It seems that the most effective approach concerning the avoidance of bleeding among patients with chemotherapy-induced thrombocytopenia would be the development of new cancer treatments that would not cause thrombocytopenia.
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