Molecular mechanisms of cytoadherence in malaria

1999 ◽  
Vol 276 (6) ◽  
pp. C1231-C1242 ◽  
Author(s):  
May Ho ◽  
Nicholas J. White
Keyword(s):  
Adhesion Molecule ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Multiorgan Failure ◽  
Host Cells ◽  
Microbial Pathogens ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Metabolic Disturbances ◽  
Adhesive Interactions

Microbial pathogens subvert host adhesion molecules to disseminate or to enter host cells to promote their own survival. One such subversion is the cytoadherence of Plasmodium falciparum-infected erythrocytes (IRBC) to vascular endothelium, which protects the parasite from being removed by the spleen. The process results in microcirculatory obstruction and subsequent hypoxia, metabolic disturbances, and multiorgan failure, which are detrimental to the host. Understanding the molecular events involved in these adhesive interactions is therefore critical both in terms of pathogenesis and implications for therapeutic intervention. Under physiological flow conditions, cytoadherence occurs in a stepwise fashion through parasite ligands expressed on the surface of IRBC and the endothelial receptors CD36, intercellular adhesion molecule-1 (ICAM-1), P-selectin, and vascular adhesion molecule-1. Moreover, rolling on ICAM-1 and P-selectin increases subsequent adhesion to CD36, indicating that receptors can act synergistically. Cytoadherence may activate intracellular signaling pathways in both endothelial cells and IRBC, leading to gene expression of mediators such as cytokines, which could modify the outcome of the infection.

scholarly journals Targeted gene deletion demonstrates that the cell adhesion molecule ICAM-4 is critical for erythroblastic island formation

Blood ◽  
2006 ◽  
Vol 108 (6) ◽  
pp. 2064-2071 ◽  
Author(s):  
Gloria Lee ◽  
Annie Lo ◽  
Sarah A. Short ◽  
Tosti J. Mankelow ◽  
Frances Spring ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Molecular Mechanisms ◽  
Intercellular Adhesion Molecule ◽  
Immunoglobulin Superfamily ◽  
Erythroid Progenitors ◽  
Island Formation ◽  
Knock Out ◽  
Erythroblastic Island ◽  
Adhesive Interactions ◽  
Knock Out Mice

AbstractErythroid progenitors differentiate in erythroblastic islands, bone marrow niches composed of erythroblasts surrounding a central macrophage. Evidence suggests that within islands adhesive interactions regulate erythropoiesis and apoptosis. We are exploring whether erythroid intercellular adhesion molecule 4 (ICAM-4), an immunoglobulin superfamily member, participates in island formation. Earlier, we identified αV integrins as ICAM-4 counterreceptors. Because macrophages express αV, ICAM-4 potentially mediates island attachments. To test this, we generated ICAM-4 knock-out mice and developed quantitative, live cell techniques for harvesting intact islands and for re-forming islands in vitro. We observed a 47% decrease in islands reconstituted from ICAM-4 null marrow compared to wild-type marrow. We also found a striking decrease in islands formed in vivo in knock-out mice. Further, peptides that block ICAM-4/αV adhesion produced a 53% to 57% decrease in reconstituted islands, strongly suggesting that ICAM-4 binding to macrophage αV functions in island integrity. Importantly, we documented that αV integrin is expressed in macrophages isolated from erythroblastic islands. Collectively, these data provide convincing evidence that ICAM-4 is critical in erythroblastic island formation via ICAM-4/αV adhesion and also demonstrate that the novel experimental strategies we developed will be valuable in exploring molecular mechanisms of erythroblastic island formation and their functional role in regulating erythropoiesis.

scholarly journals Intraluminal crawling of neutrophils to emigration sites: a molecularly distinct process from adhesion in the recruitment cascade

2006 ◽  
Vol 203 (12) ◽  
pp. 2569-2575 ◽  
Author(s):  
Mia Phillipson ◽  
Bryan Heit ◽  
Pina Colarusso ◽  
Lixin Liu ◽  
Christie M. Ballantyne ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Molecular Mechanisms ◽  
Time Lapse ◽  
Intercellular Adhesion ◽  
Video Microscopy ◽  
Intercellular Adhesion Molecule ◽  
Wild Type ◽  
Intercellular Adhesion Molecule 1 ◽  
Inflammatory Protein

The prevailing view is that the β2-integrins Mac-1 (αMβ2, CD11b/CD18) and LFA-1 (αLβ2, CD11a/CD18) serve similar biological functions, namely adhesion, in the leukocyte recruitment cascade. Using real-time and time-lapse intravital video-microscopy and confocal microscopy within inflamed microvessels, we systematically evaluated the function of Mac-1 and LFA-1 in the recruitment paradigm. The chemokine macrophage inflammatory protein-2 induced equivalent amounts of adhesion in wild-type and Mac-1−/− mice but very little adhesion in LFA-1−/− mice. Time-lapse video-microscopy within the postcapillary venules revealed that immediately upon adhesion, there is significant intraluminal crawling of all neutrophils to distant emigration sites in wild-type mice. In dramatic contrast, very few Mac-1−/− neutrophils crawled with a 10-fold decrease in displacement and a 95% reduction in velocity. Therefore, Mac-1−/− neutrophils initiated transmigration closer to the initial site of adhesion, which in turn led to delayed transmigration due to movement through nonoptimal emigration sites. Interestingly, the few LFA-1−/− cells that did adhere crawled similarly to wild-type neutrophils. Intercellular adhesion molecule-1 but not intercellular adhesion molecule-2 mediated the Mac-1–dependent crawling. These in vivo results clearly delineate two fundamentally different molecular mechanisms for LFA-1 and Mac-1 in vivo, i.e., LFA-1–dependent adhesion followed by Mac-1–dependent crawling, and both steps ultimately contribute to efficient emigration out of the vasculature.

Role of macrophage SR-BI class a scavenger receptor in atherosclerosis: Crosstalk TLR4/NF-KB/ signaling pathway activation   

2019 ◽  
Vol 7 (4) ◽  
pp. 298-309
Author(s):  
Jilin Wang ◽  
Jeffrey D. Juan
Keyword(s):  
Signaling Pathways ◽  
Adhesion Molecule ◽  
Intracellular Signaling ◽  
Scavenger Receptor ◽  
Cell Types ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Inflammatory Stimuli ◽  
Class B ◽  
Tlr4 Activation

Atherosclerosis is an inflammatory disease, and one of the culprits may be infections caused by pathogens, that may be linked to development and progression of atherosclerosis by several mechanisms. Class B scavenger receptor BI (SR-BI), an HDL receptor, SR-BI is expressed in a variety of cell types, most abundantly in steroidogenic cells and in the liver. SR-BI is also expressed in macrophages has been shown to mediate the cellular uptake of certain bacteria and may therefore play an important role in innate immunity. The innate immune response and the homeostatic network controlling cellular sterol are important implications for several common diseases, including atherosclerosis. The TLR4-independent SR-BI signaling in macrophages and the implication for its role in atherosclerosis has not yet to be investigated. Our data showed that mice lacking SR-BI are highly sensitive to form atherosclerosis than wild type mice. In addition, we showed that SR-BI-/- mice attenuated proinflammatory cytokines and chemokine response to LPS. The LPS-induced cytokine expression in both WT and SR-BI-/- was dependent on NFκB signaling pathways. One possibility is that an interaction between SR-BI and the TLR4 complex might modulate TLR4 activation and subsequent intracellular signaling pathways. The interaction of HDL and SR-BI in endothelial cells inhibits the activation of NFκB and subsequent expression of the adhesion molecules vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 to inflammatory stimuli. We conclude that SR-BI plays an important function in the atherosclerosis mechanism.

scholarly journals Lymphocyte-Fibroblast Interactions

1997 ◽  
Vol 8 (1) ◽  
pp. 40-50 ◽  
Author(s):  
S. Murakami ◽  
H. Okada
Keyword(s):  
Connective Tissue ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Fibroblast Cell ◽  
Intercellular Adhesion Molecule ◽  
Lymphocyte Function ◽  
Tissue Destruction ◽  
Intercellular Adhesion Molecule 1 ◽  
Inflammatory Reactions ◽  
Adhesive Interactions

Chronic inflammatory reactions are usually characterized by inflammatory cell accumulation in the extravascular connective tissue. In such sites, inappropriate activation of circulating or resident lymphocytes becomes self-perpetuating and can lead to chronic tissue destruction. In addition to that, the locally infiltrated lymphocytes should have an opportunity to interact directly with fibroblasts composing the connective tissue. The direct interactions of those different cell types seem to play important roles in lymphocyte lodging and retention in such sites. Thus, for clarification of the immunopathogenesis of the chronic inflammatory diseases, including periodontitis, it is important that the molecular mechanisms involved in the heterotypic cell-cell interactions be revealed. In fact, it has been demonstrated that lymphocytes interact with various non-hematopoietic cells, such as epithelial cells and endothelial cells. Regarding interactions with fibroblasts, it has been shown that IFNγ-stimulated fibroblasts can regulate the proliferative responses of T-lymphocytes both positively and negatively. Furthermore, activated lymphocytes have demonstrated strong binding ability to various fibroblast cell lines. Blocking experiments utilizing monoclonal antibodies specific to various cell adhesion molecules revealed that very late antigen (VLA) integrins, lymphocyte-function-associated antigen (LFA-1)/intercellular adhesion molecule-1 (ICAM-1), CD44/hyarulonate are, at least in part, involved in lymphocyte-fibroblast interactions. In addition, recent findings raised the possibility that the adhesive interactions between lymphocytes and fibroblasts influenced the various cellular functions of each cell type. In fact, it was recently demonstrated that the adhesive interactions stimulated fibroblasts to increase expression of inflammatory cytokine mRNA. These results strongly suggest that fibroblasts are not merely innocent bystanders but actively participate in local inflammatory reactions by directly interacting with locally infiltrated lymphocytes.

XO increases neutrophil adherence to endothelial cells by a dual ICAM-1 and P-selectin-mediated mechanism

1997 ◽  
Vol 82 (3) ◽  
pp. 866-873 ◽  
Author(s):  
Lance S. Terada ◽  
Brooks M. Hybertson ◽  
Kevin G. Connelly ◽  
David Weill ◽  
Dale Piermattei ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Platelet Activating Factor ◽  
Surface Expression ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Neutrophil Adherence ◽  
Adhesive Interactions ◽  
Static Conditions

Terada, Lance S., Brooks M. Hybertson, Kevin G. Connelly, David Weill, Dale Piermattei, and John E. Repine. XO increases neutrophil adherence to endothelial cells by a dual ICAM-1 and P-selectin-mediated mechanism. J. Appl. Physiol. 82(3): 866–873, 1997.—Circulating xanthine oxidase (XO) can modify adhesive interactions between neutrophils and the vascular endothelium, although the mechanisms underlying this effect are not clear. We found that treatment with XO of bovine pulmonary artery endothelial cells (EC), but not neutrophils or plasma, increased adherence, suggesting that XO had its primary effect on EC. The mechanism by which XO increased neutrophil adherence to EC involved binding of XO to EC and production of H2O2. XO also increased platelet-activating factor production by EC by a H2O2-dependent mechanism. Similarly, the platelet-activating factor-receptor antagonist WEB-2086 completely blocked XO-mediated neutrophil EC adherence. In addition, neutrophil adherence was dependent on the β2-integrin Mac-1 (CD11b/CD18) but not on leukocyte functional antigen-1 (CD11a/CD18). Treatment of EC with XO for 30 min did not alter intercellular adhesion molecule-1 surface expression but increased expression of P-selectin and release of von Willibrand factor. Antibodies against P-selectin (CD62) did not affect XO-mediated neutrophil adherence under static conditions but decreased both rolling and firm adhesive interactions under conditions of shear. We conclude that extracellular XO associates with the endothelium and promotes neutrophil-endothelial cell interactions through dual intercellular adhesion molecule-1 and P-selectin ligation, by a mechanism that involves platelet-activating factor and H2O2as intermediates.

scholarly journals Monocyte adhesion to cerebromicrovascular endothelial cells derived from hypertensive and normotensive rats

1994 ◽  
Vol 267 (6) ◽  
pp. H2491-H2497 ◽  
Author(s):  
R. M. McCarron ◽  
L. Wang ◽  
A. L. Siren ◽  
M. Spatz ◽  
J. M. Hallenbeck
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Interleukin 1 ◽  
Intercellular Adhesion Molecule ◽  
Monocyte Adhesion ◽  
Blood Monocytes ◽  
Intercellular Adhesion Molecule 1 ◽  
Necrosis Factor Alpha ◽  
Stroke Risk Factor ◽  
Adhesive Interactions

The stroke risk factor hypertension may function as a predisposing agent by increasing the vulnerability of blood vessels to thrombosis or hemorrhage. The research here demonstrates that cerebrovascular endothelial cells (EC) from spontaneously hypertensive (SHR) and Wistar-Kyoto normotensive (WKY) rats exhibit similar levels of adhesiveness for syngeneic peripheral blood monocytes (e.g., 22.53 +/- 1.32 and 24.35 +/- 1.16%, respectively). Monocyte adhesion to SHR EC was dramatically increased by treatment of EC with lipopolysaccharide, interferon-gamma, or interleukin-1 beta and tumor necrosis factor-alpha (e.g., 106, 68, and 171%, respectively). Identical treatment of WKY EC also increased adhesion albeit at significantly lower levels than observed on concomitantly tested SHR EC (e.g., 47.8, 12.7, and 60.7%, respectively). Allogeneic combinations of monocytes and EC again demonstrated significantly more upregulation of adhesion by treatment of SHR EC than WKY EC. Characterization of these adhesive interactions revealed the interplay of adhesion pathways, which include lymphocyte functional antigen-1/intercellular adhesion molecule-1 (ICAM-1), Mac-1/ICAM-1, and very late activation antigen-4/vascular adhesion molecule-1 as well as other undetermined mechanisms. In summary, these findings indicate hypertension may enhance responsiveness of endothelium to factors that promote monocyte adhesion.

Paraoxonase-1 and myeloperoxidase correlate with vascular biomarkers in overweight patients with newly diagnosed untreated hyperlipidaemia

VASA ◽  
2017 ◽  
Vol 46 (5) ◽  
pp. 370-376 ◽  
Author(s):  
Anita Szentpéteri ◽  
Noémi Zsíros ◽  
Viktória E. Varga ◽  
Hajnalka Lőrincz ◽  
Mónika Katkó ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Oxidized Ldl ◽  
Vascular Complications ◽  
Cd40 Ligand ◽  
Paraoxonase 1 ◽  
Intercellular Adhesion Molecule ◽  
Pon1 Activity ◽  
Intercellular Adhesion Molecule 1 ◽  
Inflammatory Parameters ◽  
Vascular Biomarkers

Abstract. Background: In hyperlipidaemic state, increased levels of myeloperoxidase (MPO) and decreased paraoxonase-1 (PON1) activity have been reported; however, their relationships with other atherosclerotic biomarkers have not been completely clarified. Patients and methods: Serum concentrations of lipid and inflammatory parameters, MPO levels, and PON1 activities were investigated in 167 untreated hyperlipidaemic patients with and without vascular complications and in 32 healthy controls. Additionally, levels of CD40 ligand (sCD40L) and asymmetric dimethyl arginine (ADMA), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1, and oxidized LDL were determined. Results: We found elevated C-reactive protein (CRP), ADMA, sCD40L, sICAM-1 concentrations, and higher MPO levels in patients with vascular complications compared to those without. The PON1 arylesterase activity correlated negatively with sCD40L, ADMA, and sICAM-1 levels, respectively. In contrast, MPO concentrations showed positive correlations with sCD40L, ADMA, and sICAM-1 levels, respectively. Conclusions: It can therefore be stated that PON1 activity and MPO level correlate strongly with the vascular biomarkers, highlighting the importance of the HDL-associated pro- and antioxidant enzymes in the development of endothelial dysfunction and atherogenesis.

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