scholarly journals Knob-independent cytoadherence of Plasmodium falciparum to the leukocyte differentiation antigen CD36.

1990 ◽  
Vol 171 (6) ◽  
pp. 1883-1892 ◽  
Author(s):  
B A Biggs ◽  
L Goozé ◽  
K Wycherley ◽  
D Wilkinson ◽  
A W Boyd ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Peripheral Circulation ◽  
Melanoma Cells ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Differentiation Antigen ◽  
Erythrocyte Surface ◽  
Falciparum Erythrocyte Membrane Protein

The survival of Plasmodium falciparum-infected erythrocytes is enhanced by the sequestration of mature trophozoites and schizonts from the peripheral circulation. Cytoadherence of infected erythrocytes in vivo is associated with the presence of knobs on the erythrocyte surface, but we and others have shown recently that cytoadherence to C32 melanoma cells may occur in vitro in the absence of knobs. We show here that a knobless clone of P. falciparum adheres to the leukocyte differentiation antigen, CD36, suggesting that binding to CD36 is independent of the presence of knobs on the surface of the infected erythrocyte. This clone showed little cytoadherence to immobilized thrombospondin or to endothelial cells expressing the intercellular adhesion molecule 1. Furthermore, an Mr approximately 300-kD trypsin-sensitive protein doublet was immunoprecipitated from knobless trophozoite-infected erythrocytes. Finding a P. falciparum erythrocyte membrane protein 1 (PfEMP1)-like molecule on these infected erythrocytes is consistent with a role for PfEMP1 in cytoadherence to CD36 and C32 melanoma cells.

Characterization of Plasmodium falciparum-Infected Erythrocyte and P-Selectin Interaction Under Flow Conditions

Blood ◽  
1998 ◽  
Vol 91 (12) ◽  
pp. 4803-4809 ◽  
Author(s):  
May Ho ◽  
Tineke Schollaardt ◽  
Xiaofei Niu ◽  
Sornchai Looareesuwan ◽  
Kamala D. Patel ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Adhesion Molecule ◽  
Sialic Acid Residue ◽  
Intercellular Adhesion Molecule ◽  
Flow Conditions ◽  
Intercellular Adhesion Molecule 1 ◽  
Adhesive Interaction ◽  
Lectin Domain

Abstract Plasmodium falciparum-infected erythrocytes (IRBC) roll on the adhesion molecule P-selectin in vitro under flow conditions that approximate the shear stress in capillary and postcapillary venules in which cytoadherence occurs in vivo. The pathological significance of this adhesive interaction is currently unknown. In this study, we further investigated the molecular interactions between IRBC and P-selectin by using a laminar flow system that allowed for the direct visualization of IRBC-substratum interactions. The results showed that the IRBC–P-selectin interaction was Ca2+-dependent and involved the lectin domain of P-selectin and a sialic acid residue on IRBC. The sialylated P-selectin ligand was trypsin-sensitive, which suggests that it could be part of the parasite antigen PfEMP1 that interacts with CD36 and intercellular adhesion molecule-1 (ICAM-1), but different from a trypsin-resistant IRBC ligand that adheres selectively to chondroitin sulfate A. Studies on the rolling and adhesion of IRBC on activated platelets that express both CD36 and P-selectin showed that inhibition of rolling on P-selectin reduced the adhesion of some clinical parasite isolates to CD36, whereas other parasite isolates appeared to interact directly with CD36. Thus, cytoadherence under physiological flow conditions may be mediated by multiple IRBC ligands that interact with different adhesion molecules in a cooperative fashion. These findings underscore the complexity of the interactions betweeen IRBC and vascular endothelium.

Recombinant PfEMP1 peptide inhibits and reverses cytoadherence of clinical Plasmodium falciparum isolates in vivo

Blood ◽  
2003 ◽  
Vol 101 (1) ◽  
pp. 331-337 ◽  
Author(s):  
Bryan G. Yipp ◽  
Dror I. Baruch ◽  
Ciaran Brady ◽  
Allan G. Murray ◽  
Sornchai Looareesuwan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Severe Combined Immunodeficiency ◽  
Inhibitory Effect ◽  
Intercellular Adhesion Molecule ◽  
Skin Grafts ◽  
Intercellular Adhesion Molecule 1 ◽  
Recombinant Peptide ◽  
Tnf Α

Abstract The parasite ligand Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) and host endothelial receptors represent potential targets for antiadhesive therapy for cytoadherence. In the present study, the major host receptor CD36 was targeted in vitro and in vivo with a recombinant peptide, PpMC-179, corresponding to the minimal CD36-binding domain from the cysteine-rich interdomain region 1 (CIDR1) within the MCvar1 PfEMP1. The in vitro inhibitory effect of PpMC-179 on human dermal microvascular endothelial cells (HDMECs) expressing multiple relevant adhesion molecules was investigated using a parallel-plate flow chamber. Pretreatment of endothelial monolayers with PpMC-179 (2 μM) inhibited the adhesion of infected erythrocytes (IRBCs) from all clinical isolates tested by 84.4% on resting and 62.8% on tumor necrosis factor α (TNF-α)–stimulated monolayers. Adhesion to stimulated cells was further inhibited (90.4%) when PpMC-179 was administered with an inhibitory anti–intercellular adhesion molecule 1 (ICAM-1) monoclonal antibody 84H10 (5 μg/mL). To determine the in vivo effectiveness of PpMC-179, we used a human/severe combined immunodeficiency (SCID) mouse chimeric model that allowed direct visualization of cytoadherence on intact human microvasculature. In unstimulated skin grafts, PpMC-179 inhibited adhesion by 86.3% and by 84.6% in TNF-α–stimulated skin grafts. More importantly, PpMC-179 administration resulted in the detachment of already adherent IRBCs by 80.7% and 83.3% on resting and stimulated skin grafts, respectively. The antiadhesive effect of PpMC-179 was rapid and sustained in vivo for at least 30 minutes. Our data indicate that targeting cytoadhesion in vivo is feasible and may offer a rapid antimalarial therapy.

Characterization of Plasmodium falciparum-Infected Erythrocyte and P-Selectin Interaction Under Flow Conditions

Blood ◽  
1998 ◽  
Vol 91 (12) ◽  
pp. 4803-4809 ◽  
Author(s):  
May Ho ◽  
Tineke Schollaardt ◽  
Xiaofei Niu ◽  
Sornchai Looareesuwan ◽  
Kamala D. Patel ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Adhesion Molecule ◽  
Sialic Acid Residue ◽  
Intercellular Adhesion Molecule ◽  
Flow Conditions ◽  
Intercellular Adhesion Molecule 1 ◽  
Adhesive Interaction ◽  
Lectin Domain

Plasmodium falciparum-infected erythrocytes (IRBC) roll on the adhesion molecule P-selectin in vitro under flow conditions that approximate the shear stress in capillary and postcapillary venules in which cytoadherence occurs in vivo. The pathological significance of this adhesive interaction is currently unknown. In this study, we further investigated the molecular interactions between IRBC and P-selectin by using a laminar flow system that allowed for the direct visualization of IRBC-substratum interactions. The results showed that the IRBC–P-selectin interaction was Ca2+-dependent and involved the lectin domain of P-selectin and a sialic acid residue on IRBC. The sialylated P-selectin ligand was trypsin-sensitive, which suggests that it could be part of the parasite antigen PfEMP1 that interacts with CD36 and intercellular adhesion molecule-1 (ICAM-1), but different from a trypsin-resistant IRBC ligand that adheres selectively to chondroitin sulfate A. Studies on the rolling and adhesion of IRBC on activated platelets that express both CD36 and P-selectin showed that inhibition of rolling on P-selectin reduced the adhesion of some clinical parasite isolates to CD36, whereas other parasite isolates appeared to interact directly with CD36. Thus, cytoadherence under physiological flow conditions may be mediated by multiple IRBC ligands that interact with different adhesion molecules in a cooperative fashion. These findings underscore the complexity of the interactions betweeen IRBC and vascular endothelium.

Expression and self-regulatory function of cardiac interleukin-6 during endotoxemia

2000 ◽  
Vol 279 (5) ◽  
pp. H2241-H2248 ◽  
Author(s):  
Hiroshi Saito ◽  
Cam Patterson ◽  
Zhaoyong Hu ◽  
Marschall S. Runge ◽  
Ulka Tipnis ◽  
...  
Keyword(s):  
Feedback Mechanism ◽  
Intercellular Adhesion Molecule ◽  
Regulatory Function ◽  
Heart Cells ◽  
Intercellular Adhesion Molecule 1 ◽  
Negative Feedback Mechanism ◽  
Proinflammatory Mediators ◽  
Tnf Α

Interleukin (IL)-6 reportedly has negative inotropic and hypertrophic effects on the heart. Here, we describe endotoxin-induced IL-6 in the heart that has not previously been well characterized. An intraperitoneal injection of a bacterial lipopolysaccharide into C57BL/6 mice induced IL-6 mRNA in the heart more strongly than in any other tissue examined. Induction of mRNA for two proinflammatory cytokines, IL-1β and tumor necrosis factor (TNF)-α, occurred rapidly before the induction of IL-6 mRNA and protein. Although stimulation of isolated rat neonatal myocardial cells with IL-1β or TNF-α induced IL-6 mRNA in vitro, nonmyocardial heart cells produced higher levels of IL-6 mRNA upon stimulation with IL-1β. In situ hybridization and immunohistochemical analyses localized the IL-6 expression primarily in nonmyocardial cells in vivo. Endotoxin-induced expression of cardiac IL-1β, TNF-α, and intercellular adhesion molecule 1 was augmented in IL-6-deficient mice compared with control mice. Thus cardiac IL-6, expressed mainly by nonmyocardial cells via IL-1β action during endotoxemia, is likely to suppress expression of proinflammatory mediators and to regulate itself via a negative feedback mechanism.

scholarly journals Monoclonal antibody to the interferon-inducible protein Leu-13 triggers aggregation and inhibits proliferation of leukemic B cells

Blood ◽  
1990 ◽  
Vol 76 (12) ◽  
pp. 2583-2593 ◽  
Author(s):  
SS Evans ◽  
DB Lee ◽  
T Han ◽  
TB Tomasi ◽  
RL Evans
Keyword(s):  
B Cells ◽  
Dna Synthesis ◽  
Lymphocytic Leukemia ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Adhesive Properties ◽  
Prolymphocytic Leukemia ◽  
Ifn Alpha

Abstract Interferon (IFN)-alpha inhibits DNA synthesis stimulated by low molecular weight B-cell growth factor (BCGF) in hairy cells in vitro, suggesting that the therapeutic efficacy of IFN-alpha in hairy cell leukemia (HCL) involves growth inhibition of malignant B cells. Evidence that the 16-Kd cell surface protein Leu-13 mediates an antiproliferative signal in T lymphocytes and is IFN-inducible in endothelial cells prompted us to examine the expression and functional role of this molecule in leukemic B cells. Leu-13 density, determined by flow cytometry, was upregulated in vitro and in vivo by IFN-alpha on malignant B cells from patients with HCL, chronic lymphocytic leukemia, and prolymphocytic leukemia. Monoclonal anti-Leu-13 triggered homotypic aggregation of leukemic B cells via an adhesion pathway that was not inhibited by antibodies to leukocyte function associated antigen-1 (LFA- 1) or intercellular adhesion molecule-1 (ICAM-1). Moreover, anti-Leu-13 potentiated the inhibitory effects of IFN-alpha on BCGF-stimulated DNA synthesis, assessed by [3H]-thymidine and [3H]-deoxyadenosine incorporation into DNA. These results indicate that Leu-13 is part of a novel IFN-inducible signaling pathway which may modify the growth and adhesive properties of leukemic B cells under physiologic or therapeutic conditions.

Mechanism by which H-2g, a glucose analog of blood group H antigen, mediates angiogenesis

Blood ◽  
2005 ◽  
Vol 105 (6) ◽  
pp. 2343-2349 ◽  
Author(s):  
Kui Zhu ◽  
Mohammed Asif Amin ◽  
Yuanyuan Zha ◽  
Lisa A. Harlow ◽  
Alisa E. Koch
Keyword(s):  
Growth Factor ◽  
Critical Role ◽  
Aortic Ring ◽  
Nuclear Factor Κb ◽  
Janus Kinase ◽  
Intercellular Adhesion Molecule ◽  
Soluble Form ◽  
Intercellular Adhesion Molecule 1

AbstractThe 4A11 antigen is a unique cytokine-inducible antigen up-regulated on rheumatoid arthritis (RA) synovial endothelial cells (ECs) compared with normal ECs. Previously, we showed that in soluble form, this antigen, Lewisy-6/H-5-2 (Ley/H) or its glucose analog, 2-fucosyl lactose (H-2g), induced the expression of EC intercellular adhesion molecule-1 (ICAM-1) and leukocyte-endothelial adhesion through the Janus kinase 2 (JAK2)–signal transducer and activator of transcription 3 (STAT3) pathway. Currently, we show that H-2g induces release of EC angiogenic basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), an effect inhibited by decoy nuclear factor κB (NFκB) oligodeoxynucleotide (ODN). JAK2 and phosphoinositide-3 kinase (PI3K) are 2 upstream kinases of NFκB activated by H-2g, as confirmed by an inhibitor of kappa B kinase (IKKβ) assay. In vitro, H-2g induces vascular sprouting in the rat aortic ring model, whereas blockade of JAK2, PI3K, or NFκB inhibits sprouting. Likewise, in the in vivo mouse Matrigel plug angiogenesis assay, chemical inhibitors and antisense or decoy ODNs of JAK2, PI3K, or NFκB decrease angiogenesis, confirming the importance of these pathways in H-2g–induced EC signaling. The critical role of Ley/H involvement in angiogenesis and its signaling pathways may provide new targets for therapy of diseases characterized by pathologic neovascularization.

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