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Inflammation and immunology
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
Christopher Bellamy, Stephen J. Jenkins, Henry J. McSorley, David A. Dorward, Timothy J. Kendall
Obviously, the response of endothelial cells on activation adjacent to tissue injury is critical in signalling to leukocytes in the circulation. Expression of cell adhesion molecules is controlled in several different ways in these cell types. Molecules such as P-selectin are stored preformed in endothelial cells in Weibel–Palade bodies. On stimulation of the endothelial cells by histamine or platelet-activating factor (PAF), the P-selectin within these cytoplasmic storage granules is rapidly redistributed to the cell surface within minutes. Thus the expression of P-selectin on the endothelium is an important early mechanism for attracting leukocytes to a site of inflammation. Other adhesion molecules, including E-selectin, ICAM-1, and VCAM-1, are expressed by new protein synthesis. On stimulation of the endothelial cells by proinflammatory cytokines such as TNF or interleukin 1 (IL-1) there is transcriptional activation of the genes encoding these proteins. This level of control of adhesion molecules requires between 4 and 6 hours of stimulation but can be sustained for hours or days.
Host Defense I: Non-specific Immunity
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
The last group of adhesion molecules is the selectin family (LEC-CAMs). These molecules resemble lectins and bind to carbohydrate ligands. Most of these are important in lymphocyte homing to various tissues and are also known as addressins. L-selectin(CD62L, also called LAM-1), is expressed on T and B cells, NK cells, neutrophils, and monocyte derivatives. On the lymphocyte surface LAM-1 directs cells to HEV of peripheral lymph nodes. P-selectin (CD62P) is a component of platelet and endothelial cell granules and mediates adhesion to neutrophils and monocytes. The carbohydrate CD 15 (Lewisx) expressed on granulocytes is a ligand for CD62P. IL-1 induces endothelial cells to express E-selectin (CD62E, ELAM-1) which binds to the carbohydrate CD15s (sialyl-Lewisx) on granulocyte membranes. Recently, a small group of patients with recurrent bacterial infections were found to have a deficiency of a fucosyltransferase enzyme which is required to generate the sialyl-Lewis X determinant. This has been called leukocyte adhesion deficiency type 2.
Regulation of Eosinophil Function by P-Selectin
Published in Gerald J. Gleich, A. Barry Kay, Eosinophils in Allergy and Inflammation, 2019
Mathew A. Vadas, C. M. Lucas, J. R. Gamble, Angel F. Lopez, M. P. Skinner, M. C. Berndt
P-selectin appears to be a physiologically relevant molecule that is expressed on endothelial cell surfaces after treatment with thrombin or histamine (10) and on platelets after activation (11). P-selectin is also found in the plasma of normal individuals (5). We found that eosinophils adhere strongly to purified P-selectin (Fig. 1) or CHO cells expressing recombinant P-selectin (Fig. 2) and that this adhesion is not associated with spreading or polarization (Figs. 3 and 4) normally associated with eosinophil activation. The adhesion was inhibitable by a polyclonal antibody against P-selectin (data not shown). In comparison to cells adherent to extracellular matrix proteins, eosinophils adherent to P-selectin were deficient in generation. Fluid-phase P-selectin also inhibited eosinophil activation even after adhesion to fibrinogen (data not shown). This suggests that P-selectin signals cells and interrupts the normal activation process. Similar inhibitory effect of fluid-phase P-selectin was observed on degranulation in response to phorbol myristate acetate but not Ig Sepharose (Fig. 6), suggesting that P-selectin does not interrupt all activation pathways. This was supported by the lack of effect of P-selectin on antibody-dependent cytotoxicity (Fig. 7).
Recurrence of acute chest syndrome post stopping Crizanlizumab, the dilemma of stopping vs continuation in patient with sickle cell disease: case report
Published in Hematology, 2023
Mohammad S. Afana, Mohammad Abu-Tineh, Awni Alshurafa, Ahmed K. Yasin, Khalid Ahmed, Mohammed Abdulgayoom, Mohamed A. Yassin
Acute chest syndrome (ACS) one of the most common causes of death in SCD is defined by the presence of new chest infiltrate on imaging with respiratory symptoms and/or fever [1,8]. Three major causes have been proposed in ACS pathophysiology: pulmonary infection, bone marrow fat embolization, and pulmonary intravascular sequestration of sickled erythrocytes [9]. After VOC, ACS is the second most common cause of hospitalizations [1]. The Underlying pathophysiology of SCD complications is complex [10]. One of these involves P-selectin; an adhesion molecule found in platelets and endothelial cells. It is activated in response to inflammation and trauma. In SCD P-Selectin upregulation contributes to VOC by the adhesion of sickle red blood cells and leukocytes to the endothelial cells [11].
Platelet-leukocyte aggregate formation and inflammation in patients with pulmonary arterial hypertension and CTEPH
Published in Platelets, 2022
Mikael Åberg, Erik Björklund, Gerhard Wikström, Christina Christersson
There are some limitations of the present study. The study cohort was collected at one center and consists of a limited number of patients within each group, which might influence the results of e.g the differences regarding PMAs or PGAs among different subgroups. The majority of the patients were treated with PAH-specific treatment, but only a crude analysis could be done regarding their effects on the number of activated platelets, platelet-leukocyte aggregates or inflammatory cytokines. Again, a larger study material is needed to clarify this. Finally, our focus on cytokine release and platelet leukocyte aggregation made us choose P-selectin as a marker for platelet activation. It is possible that another approach, such as measuring PAC-1 instead, could have shifted the results somewhat.
In vitro effects of cobalt and chromium nanoparticles on human platelet function
Published in Nanotoxicology, 2021
Dominik Taterra, Bendik Skinningsrud, Przemysław A. Pękala, Iwona M. Tomaszewska, Krzysztof Marycz, Marek W. Radomski, Krzysztof A. Tomaszewski
Aggregation of platelets due to Co and Cr NPs was observed in almost all concentrations when analyzed by aggregometry. Previous studies have shown a size-dependent effect on platelet aggregation with larger NPs causing no or less platelet aggregation when compared to smaller NPs (Santos-Martinez et al. 2012, 2015). In our study, all sizes of NPs (28–60nm) induced platelet aggregation as seen by aggregometry, however, no relation between the size of the NP and the effect on aggregation was observed with this method. While aggregometry showed no platelet aggregation due to NPs at the lowest tested concentration (5 µg/mL), flow cytometry revealed an increased abundance of P-selectin on platelet surfaces following interactions with Co 28 nm and Co2O3 50 nm NPs at this concentration. P-selectin is one of the most sensitive markers of platelet activation. Upon platelet activation, the protein P-selectin is translocated to the platelet surface and mediates the formation of platelet-leukocyte aggregates (Tomaszewski, Radomski, and Santos-Martinez 2015). We have shown that NP-induced platelet activation is associated with increased expression of P-selectin on the platelet surface membrane (Radomski et al. 2005; Santos-Martinez et al. 2012, 2015). Therefore, the increased abundance of P-selectin observed in this study strongly suggests that Co NPs activate platelets.