Leslie Parise - Academia.edu (original) (raw)

Papers by Leslie Parise

Research paper thumbnail of Platelet 21 integrin activation: contribution of ligand internalization and the 2-cytoplasmic domain

Research paper thumbnail of CIB1 Is Essential for Mouse Spermatogenesis

Molecular and Cellular Biology, 2006

Research paper thumbnail of Essential role of CIB1 in regulating PAK1 activation and cell migration

Journal of Cell Biology, 2005

Research paper thumbnail of Tickling the tails: cytoplasmic domain proteins that regulate integrin αIIbβ3 activation

Current Opinion in Hematology, 2007

Research paper thumbnail of New aspects of integrin signaling in cancer

Seminars in Cancer Biology, 2000

Research paper thumbnail of Integrins and GTPases in tumour cell growth, motility and invasion

Trends in Cell Biology, 1998

Research paper thumbnail of R-Ras Signals through Specific Integrin a Cytoplasmic Domains to Promote Migration and Invasion of Breast Epithelial Cells

Research paper thumbnail of Cdc42 and Rac1 induce integrin-mediated cell motility and invasiveness through PI(3)K

Nature, 1997

Transformation of mammary epithelial cells into invasive carcinoma results in alterations in thei... more Transformation of mammary epithelial cells into invasive carcinoma results in alterations in their integrin-mediated responses to the extracellular matrix, including a loss of normal epithelial polarization and differentiation, and a switch to a more motile, invasive phenotype. Changes in the actin cytoskeleton associated with this switch suggest that the small GTPases Cdc42 and Rac, which regulate actin organization, might modulate motility and invasion. However, the role of Cdc42 and Rac1 in epithelial cells, especially with respect to integrin-mediated events, has not been well characterized. Here we show that activation of Cdc42 and Rac1 disrupts the normal polarization of mammary epithelial cells in a collagenous matrix, and promotes motility and invasion. This motility does not require the activation of PAK, JNK, p70 S6 kinase, or Rho, but instead requires phosphatidylinositol-3-OH kinase (PI(3)K). Further, direct PI(3)K activation is sufficient to disrupt epithelial polarization and induce cell motility and invasion. PI(3)K inhibition also disrupts actin structures, suggesting that activation of PI(3)K by Cdc42 and Rac1 alters actin organization, leading to increased motility and invasiveness.

Research paper thumbnail of Cytokines and plasma factors in sickle cell disease

Current Opinion in Hematology, 2007

Plasma cytokines and related factors represent a burgeoning area of inquiry related to the pathog... more Plasma cytokines and related factors represent a burgeoning area of inquiry related to the pathogenesis in sickle cell disease. Cytokines derived from platelets, white blood cells and endothelial cells have all been implicated in the development of several sequelae of this disease. In this review, we seek to provide an overview of the noted and potentially novel roles for several key plasma factors in sickle cell disease. We also consider the putative role for those cytokines implicated by genetic analysis in sickle cell disease, but where the pathogenic, or ameliorative, role has yet to be determined. New roles for the platelet as a key mediator in the release of cytokines in sickle cell disease have recently been demonstrated. Angiogenic and inflammatory factors are also being explored in this illness. Members of the vascular endothelial growth factor and transforming growth factor-beta superfamilies have been suggested to contribute to several key events in pathogenesis of sickle cell disease, but with the promise of nitrous oxide therapy in this disorder, these cytokines merit a fresh perspective in the context of sickle cell disease. Increased understanding of the origin and pathology of cytokine levels in sickle cell disease may provide novel therapeutic approaches in the management of the disease.

Research paper thumbnail of Fibronectin bridges monocytes and reticulocytes via integrin α4β1

British Journal of Haematology, 2008

Leucocytes are emerging as critical determinants in the severity of the pathology associated with... more Leucocytes are emerging as critical determinants in the severity of the pathology associated with sickle cell disease (SCD) and recent studies have shown that they can bind to sickle red blood cells (SS RBCs). However, the mechanism of this interaction is unclear. The α4β1 integrin on monocytes and SS reticulocytes was found to mediate the interaction of these cells in in-vitro adhesion assays and in the blood of SCD patients. Plasma fibronectin (Fn), a ligand for α4β1, could link SS RBCs to monocytes, as peptides derived from both the Arg-Gly-Asp-Ser (RGDS) and CS-1 site in Fn disrupted the reticulocyte/monocyte interaction. It was further shown in whole blood that 70% of the interacting monocytes were also bound to platelets, suggesting the existence of multi-cellular aggregates in SCD. Platelet inclusion in these aggregates was mediated by a P-selectin/P-selectin glycoprotein ligand-1 interaction, which has been demonstrated to activate the monocyte. These results suggest a new model for understanding the mechanism of attachment of SS RBCs to monocytes and implicate the platelet as a component and contributor to potentially occlusive aggregates that circulate in the blood of SCD patients.

Research paper thumbnail of Epinephrine acts through erythroid signaling pathways to activate sickle cell adhesion to endothelium via LW-v3 interactions

Research paper thumbnail of Role of Rap1 in promoting sickle red blood cell adhesion to laminin via BCAM/LU

Research paper thumbnail of Sickle Cell Adhesion to Laminin: Potential Role for the alpha 5 Chain

Research paper thumbnail of Activation-dependent changes in human platelet PECAM-1: phosphorylation, cytoskeletal association, and surface membrane redistribution

Journal of Cell Biology, 1992

Research paper thumbnail of Structure and function of platelet αllbβ3

Current Opinion in Hematology, 1997

ABSTRACT

Research paper thumbnail of Integrin-associated protein is an adhesion receptor on sickle red blood cells for immobilized thrombospondin

Research paper thumbnail of Novel epinephrine and cyclic AMP-mediated activation of BCAM/Lu-dependent sickle (SS) RBC adhesion

Research paper thumbnail of Phase I study of eptifibatide in patients with sickle cell anaemia

British Journal of Haematology, 2007

The αIIbβ3 antagonist eptifibatide is an effective treatment for patients with acute coronary syn... more The αIIbβ3 antagonist eptifibatide is an effective treatment for patients with acute coronary syndromes (ACS). Platelet reactivity and CD40 ligand (CD40L) may play a role in the pathophysiology of sickle cell anaemia (SCA) similar to that in ACS, suggesting that inhibition of platelet aggregation and CD40L release by eptifibatide may benefit patients with SCA. Following eptifibatide infusion, safety and pharmacodynamic data were obtained from four SCA patients in their non-crisis, steady states. Eptifibatide was well tolerated, with no adverse changes in the haematological, biochemical or coagulation parameters studied. Eptifibatide did not increase plasma levels of platelet factor 4 or beta-thromboglobulin, P-selectin exposure or platelet:leucocyte aggregate formation. Moreover, decreases in platelet aggregation and soluble CD40L (sCD40L) levels achieved in SCA patients were comparable to those observed in the treatment of ACS. Finally, indicators of inflammation, macrophage inflammatory protein-1α, tumour necrosis factor-α and myoglobin were reduced following eptifibatide infusion, while vasodilation correlatives, matrix metalloproteinases (MMP-2 and MMP-9) and leptin were increased. Based on these phase I results, eptifibatide may benefit SCA patients by inhibiting platelet aggregation, decreasing sCD40L levels and favourably altering plasma levels of inflammatory mediators.

Research paper thumbnail of Calcium-dependent properties of CIB binding to the integrin αIIb cytoplasmic domain and translocation to the platelet cytoskeleton

Biochemical Journal, 1999

Research paper thumbnail of Activation of sickle red blood cell adhesion via integrin-associated protein/CD47–induced signal transduction

Journal of Clinical Investigation, 2001

Research paper thumbnail of Platelet 21 integrin activation: contribution of ligand internalization and the 2-cytoplasmic domain

Research paper thumbnail of CIB1 Is Essential for Mouse Spermatogenesis

Molecular and Cellular Biology, 2006

Research paper thumbnail of Essential role of CIB1 in regulating PAK1 activation and cell migration

Journal of Cell Biology, 2005

Research paper thumbnail of Tickling the tails: cytoplasmic domain proteins that regulate integrin αIIbβ3 activation

Current Opinion in Hematology, 2007

Research paper thumbnail of New aspects of integrin signaling in cancer

Seminars in Cancer Biology, 2000

Research paper thumbnail of Integrins and GTPases in tumour cell growth, motility and invasion

Trends in Cell Biology, 1998

Research paper thumbnail of R-Ras Signals through Specific Integrin a Cytoplasmic Domains to Promote Migration and Invasion of Breast Epithelial Cells

Research paper thumbnail of Cdc42 and Rac1 induce integrin-mediated cell motility and invasiveness through PI(3)K

Nature, 1997

Transformation of mammary epithelial cells into invasive carcinoma results in alterations in thei... more Transformation of mammary epithelial cells into invasive carcinoma results in alterations in their integrin-mediated responses to the extracellular matrix, including a loss of normal epithelial polarization and differentiation, and a switch to a more motile, invasive phenotype. Changes in the actin cytoskeleton associated with this switch suggest that the small GTPases Cdc42 and Rac, which regulate actin organization, might modulate motility and invasion. However, the role of Cdc42 and Rac1 in epithelial cells, especially with respect to integrin-mediated events, has not been well characterized. Here we show that activation of Cdc42 and Rac1 disrupts the normal polarization of mammary epithelial cells in a collagenous matrix, and promotes motility and invasion. This motility does not require the activation of PAK, JNK, p70 S6 kinase, or Rho, but instead requires phosphatidylinositol-3-OH kinase (PI(3)K). Further, direct PI(3)K activation is sufficient to disrupt epithelial polarization and induce cell motility and invasion. PI(3)K inhibition also disrupts actin structures, suggesting that activation of PI(3)K by Cdc42 and Rac1 alters actin organization, leading to increased motility and invasiveness.

Research paper thumbnail of Cytokines and plasma factors in sickle cell disease

Current Opinion in Hematology, 2007

Plasma cytokines and related factors represent a burgeoning area of inquiry related to the pathog... more Plasma cytokines and related factors represent a burgeoning area of inquiry related to the pathogenesis in sickle cell disease. Cytokines derived from platelets, white blood cells and endothelial cells have all been implicated in the development of several sequelae of this disease. In this review, we seek to provide an overview of the noted and potentially novel roles for several key plasma factors in sickle cell disease. We also consider the putative role for those cytokines implicated by genetic analysis in sickle cell disease, but where the pathogenic, or ameliorative, role has yet to be determined. New roles for the platelet as a key mediator in the release of cytokines in sickle cell disease have recently been demonstrated. Angiogenic and inflammatory factors are also being explored in this illness. Members of the vascular endothelial growth factor and transforming growth factor-beta superfamilies have been suggested to contribute to several key events in pathogenesis of sickle cell disease, but with the promise of nitrous oxide therapy in this disorder, these cytokines merit a fresh perspective in the context of sickle cell disease. Increased understanding of the origin and pathology of cytokine levels in sickle cell disease may provide novel therapeutic approaches in the management of the disease.

Research paper thumbnail of Fibronectin bridges monocytes and reticulocytes via integrin α4β1

British Journal of Haematology, 2008

Leucocytes are emerging as critical determinants in the severity of the pathology associated with... more Leucocytes are emerging as critical determinants in the severity of the pathology associated with sickle cell disease (SCD) and recent studies have shown that they can bind to sickle red blood cells (SS RBCs). However, the mechanism of this interaction is unclear. The α4β1 integrin on monocytes and SS reticulocytes was found to mediate the interaction of these cells in in-vitro adhesion assays and in the blood of SCD patients. Plasma fibronectin (Fn), a ligand for α4β1, could link SS RBCs to monocytes, as peptides derived from both the Arg-Gly-Asp-Ser (RGDS) and CS-1 site in Fn disrupted the reticulocyte/monocyte interaction. It was further shown in whole blood that 70% of the interacting monocytes were also bound to platelets, suggesting the existence of multi-cellular aggregates in SCD. Platelet inclusion in these aggregates was mediated by a P-selectin/P-selectin glycoprotein ligand-1 interaction, which has been demonstrated to activate the monocyte. These results suggest a new model for understanding the mechanism of attachment of SS RBCs to monocytes and implicate the platelet as a component and contributor to potentially occlusive aggregates that circulate in the blood of SCD patients.

Research paper thumbnail of Epinephrine acts through erythroid signaling pathways to activate sickle cell adhesion to endothelium via LW-v3 interactions

Research paper thumbnail of Role of Rap1 in promoting sickle red blood cell adhesion to laminin via BCAM/LU

Research paper thumbnail of Sickle Cell Adhesion to Laminin: Potential Role for the alpha 5 Chain

Research paper thumbnail of Activation-dependent changes in human platelet PECAM-1: phosphorylation, cytoskeletal association, and surface membrane redistribution

Journal of Cell Biology, 1992

Research paper thumbnail of Structure and function of platelet αllbβ3

Current Opinion in Hematology, 1997

ABSTRACT

Research paper thumbnail of Integrin-associated protein is an adhesion receptor on sickle red blood cells for immobilized thrombospondin

Research paper thumbnail of Novel epinephrine and cyclic AMP-mediated activation of BCAM/Lu-dependent sickle (SS) RBC adhesion

Research paper thumbnail of Phase I study of eptifibatide in patients with sickle cell anaemia

British Journal of Haematology, 2007

The αIIbβ3 antagonist eptifibatide is an effective treatment for patients with acute coronary syn... more The αIIbβ3 antagonist eptifibatide is an effective treatment for patients with acute coronary syndromes (ACS). Platelet reactivity and CD40 ligand (CD40L) may play a role in the pathophysiology of sickle cell anaemia (SCA) similar to that in ACS, suggesting that inhibition of platelet aggregation and CD40L release by eptifibatide may benefit patients with SCA. Following eptifibatide infusion, safety and pharmacodynamic data were obtained from four SCA patients in their non-crisis, steady states. Eptifibatide was well tolerated, with no adverse changes in the haematological, biochemical or coagulation parameters studied. Eptifibatide did not increase plasma levels of platelet factor 4 or beta-thromboglobulin, P-selectin exposure or platelet:leucocyte aggregate formation. Moreover, decreases in platelet aggregation and soluble CD40L (sCD40L) levels achieved in SCA patients were comparable to those observed in the treatment of ACS. Finally, indicators of inflammation, macrophage inflammatory protein-1α, tumour necrosis factor-α and myoglobin were reduced following eptifibatide infusion, while vasodilation correlatives, matrix metalloproteinases (MMP-2 and MMP-9) and leptin were increased. Based on these phase I results, eptifibatide may benefit SCA patients by inhibiting platelet aggregation, decreasing sCD40L levels and favourably altering plasma levels of inflammatory mediators.

Research paper thumbnail of Calcium-dependent properties of CIB binding to the integrin αIIb cytoplasmic domain and translocation to the platelet cytoskeleton

Biochemical Journal, 1999

Research paper thumbnail of Activation of sickle red blood cell adhesion via integrin-associated protein/CD47–induced signal transduction

Journal of Clinical Investigation, 2001