Paul F. Bradfield

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OBJECTIVE A characteristic feature of the inflammatory infiltrate in rheumatoid arthritis is the segregation of CD4 and CD8 T lymphocyte subsets into distinct microdomains within the inflamed synovium. The aim of this study was to test the hypothesis that chemokines in general and stromal cell-derived factor 1 (SDF-1; CXCL12) in particular are responsible(More)
Chemokines and their receptors determine the distribution of leukocytes within tissues in health and disease. We have studied the role of the constitutive chemokine receptor CXCR4 and its ligand, stromal-derived factor-1 (SDF-1) in the perivascular accumulation of T cells in rheumatoid arthritis. We show that synovial T cells, which are primed(More)
Endothelial cell junctional adhesion molecule (JAM)-C has been proposed to regulate neutrophil migration. In the current study, we used function-blocking mAbs against human JAM-C to determine its role in human leukocyte adhesion and transendothelial cell migration under flow conditions. JAM-C surface expression in HUVEC was uniformly low, and treatment with(More)
Recent studies have shown that, in addition to its role as an adhesion receptor, platelet endothelial cell adhesion molecule 1/CD31 becomes phosphorylated on tyrosine residues Y663 and Y686 and associates with protein tyrosine phosphatases SHP-1 and SHP-2. In this study, we screened for additional proteins which associate with phosphorylated platelet(More)
Pannexin1 (Panx1) forms ATP channels that play a critical role in the immune response by reinforcing purinergic signal amplification in the immune synapse. Platelets express Panx1 and given the importance of ATP release in platelets, we investigated Panx1 function in platelet aggregation and the potential impact of genetic polymorphisms on Panx1 channels.(More)
One of the key components of the innate immune response is the recognition of microbial products such as LPS by Toll-like receptors on monocytes and neutrophils. We show here that short-term stimulation of primary human monocytes with LPS led to an increase in adhesion of monocytes to endothelial cells and a dramatic decrease in transendothelial migration(More)
Rapid mobilization of leucocytes through endothelial and epithelial barriers is key in immune system reactivity. The underlying mechanisms that regulate these processes have been the basis for many recent studies. Traditionally, leucocyte extravasation had been believed to occur through a paracellular route, which involves localized disruption of(More)
Junctional adhesion molecules (JAMs) are a family of adhesion molecules localized at the tight junction of polarized cells and on the cell surface of leukocytes. The last 20 years of research in this field has shown that several members of the family play an important role in the regulation of cell polarity, endothelium permeability and leukocytes(More)
Endothelial cells express a diverse and exquisite array of adhesion molecules and cell surface receptors. Adhesion molecules expressed on endothelial cells not only maintain structural integrity of the vasculature, but also mediate more dynamic processes such as the highly regulated movement of leukocytes from free flow into different tissue compartments.(More)
Atherosclerosis, caused in part by monocytes in plaques, continues to be a disease that afflicts the modern world. Whilst significant steps have been made in treating this chronic inflammatory disease, questions remain on how to prevent monocyte and macrophage accumulation in atherosclerotic plaques. Junctional Adhesion Molecule C (JAM-C) expressed by(More)