Infection:
Staphylococcus aureus is a major pathogen involved in endovascular infections such as infective endocarditis, suppurative thrombophlebitis, and vascular or heart valve prosthetic infection. The commencement and propagation of endovascular infections is regulated by complex interactions between surface components on the invading organism and host cells like platelets. Thus, the overall objective of our research is to investigate the effects of fluid flow on
Staphylococcus aureus blood cell interactions.
Inflammatory processes normally protect the body from infections by foreign pathogens, but when dysregulated, leukocyte migration to healthy tissues can lead to unwanted disorders and pathological conditions including, but not limited to,
ischemia-reperfusion injury, acute respiratory distress syndrome, and sometimes arthritis. Additionally, platelets can potentiate leukocyte accumulation at sites of inflammation by recruiting other free flowing leukocytes. Consequently, our research studies have focused on developing a
mechanistic understanding of leukocyte platelet-endothelial cell interactions
under physiologically relevant flow conditions.
Select Publications:
N.P.E. George,
K. Konstantopoulos, J.M. Ross, "Differential kinetics and molecular recognition mechanisms involved in early versus late growth phase S. aureus cell binding to platelets under physiological shear conditions", accepted for publication in the
Journal of Infectious Diseases 196(4); 639-646, 2007.
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N.P.E. George, Q. Wei, P.K. Shin,
K. Konstantopoulos, J.M. Ross, "Staphylococcus Aureus Adhesion via Spa, ClfA and SdrCDE to Immobilized Platelets Demonstrates Shear Dependant Behavior",
Arterioscler Thromb & Vasc Biol.
26(10); 2394-2400, 2006.
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L.H-K. Lim, M.M. Burdick, S.A. Hudson,
K. Konstantopoulos, B.S. Bochner, "Stimulation of Human Endothelium with IL-3 Induces Selective Basophil Accumulation In Vitro",
Journal of Immunology.
176(9); 5346-5353, 2006.
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A. Grazioli, C. Alves,
K. Konstantopoulos, J.T Yang, "Defective Blood Vessel Development and Pericyte/pvSMC Distribution in Alpha 4 Integrin-Deficient Mouse Embryos",
Developmental Biology.
293(1); 165-177, 2006.
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P.K. Shin, P. Pawar,
K. Konstantopoulos, J.M. Ross, "Characteristics of a New Staphylococcus aureus-RBC Adhesion Mechanism Independent of Fibrinogen and Immunoglobulin G under Hydrodynamic Shear Conditions."
American Journal of Physiology Cell Physiology.
289:C727-C734, May 2005.
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K.C. Ahn, A.J. Jun, P. Pawar, S. Jadhav, S. Napier, O.J. McCarty,
K. Konstantopoulos,
"Preferential binding of platelets to monocytes over neutrophils under flow."
Biochem Biophys Res Commun.
329(1); 345-355, April 2005.
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S. Jadhav, C.D. Eggleton, and
K. Konstantopoulos, “A 3D Computational
Model Predicts that Cell Deformation Affects Receptor-Ligand Bond Lifetime and
the Number of Bonds During Rolling Under Shear”.
Biophys J.
88(1); 96-104, Jan 2005.
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P. Pawar, P.K. Shin, S.A. Mousa, J.M. Ross, and
K. Konstantopoulos,
“Fluid Shear Regulates the Kinetics and Receptor Specifity of
Staphylococcus
Aureus Binding to Activated Platelets”,
Journal
of Immunology 173(2); 1258-1265,
2004.
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W.D. Hanley, D. Wirtz,
K. Konstantopoulos, “Distinct Kinetic and
Mechanical Properties Govern Selectin-Leukocyte Interactions”,
Journal
of Cell Science 117(12);
2503-2511, 2004.
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K. Konstantopoulos, W.D. Hanley, D. Wirtz, “Receptor/Ligand Binding:
“Catch” Bonds Finally Caught”,
Current
Biology 13; R611-R613, 2003.
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O.J.T. McCarty, N. Tien, B.S. Bochner,
K. Konstantopoulos, “Exogenous
Eosinophil Activation Converts PSGL-1-Dependent Binding to CD18-Dependent Stable
Adhesion to Platelets in Shear Flow”
American
Journal of Physiology Cell Physiology 284(5);
C1223-1234, 2003.
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M.M. Burdick, O.J.T. McCarty, S. Jadhav,
K. Konstantopoulos, “Cell-Cell
Interactions in Inflammation and Cancer Metastasis”
IEEE
Engineering in Medicine and Biology 20(3);
86-91, 2001.
M.M. Burdick, R.L. Schnaar, B.E. Collins, B.S. Bochner,
K. Konstantopoulos,
“Glycolipids Support E-selectin-Specific Strong Cell Tethering under Flow”,
Biochemical
and Biophysical Research Communications 284(1); 42-49, 2001.
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H. Tachimoto, M.M. Burdick, S.A. Hudson, M. Kikuchi,
K. Konstantopoulos,
B.S. Bochner, “CCR3-active Chemokines Promote Rapid Detachment of Eosinophils
from VCAM-1 In Vitro”
Journal of
Immunology 165(5); 2748-2754,
2000.
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