50 research outputs found
Chemokine Transfer by Liver Sinusoidal Endothelial Cells Contributes to the Recruitment of CD4+ T Cells into the Murine Liver
Leukocyte adhesion and transmigration are central features governing immune
surveillance and inflammatory reactions in body tissues. Within the liver
sinusoids, chemokines initiate the first crucial step of T-cell migration into
the hepatic tissue. We studied molecular mechanisms involved in endothelial
chemokine supply during hepatic immune surveillance and liver inflammation and
their impact on the recruitment of CD4+ T cells into the liver. In the murine
model of Concanavalin A-induced T cell-mediated hepatitis, we showed that
hepatic expression of the inflammatory CXC chemokine ligands (CXCL)9 and
CXCL10 strongly increased whereas homeostatic CXCL12 significantly decreased.
Consistently, CD4+ T cells expressing the CXC chemokine receptor (CXCR)3
accumulated within the inflamed liver tissue. In histology, CXCL9 was
associated with liver sinusoidal endothelial cells (LSEC) which represent the
first contact site for T-cell immigration into the liver. LSEC actively
transferred basolaterally internalized CXCL12, CXCL9 and CXCL10 via clathrin-
coated vesicles to CD4+ T cells leading to enhanced transmigration of CXCR4+
total CD4+ T cells and CXCR3+ effector/memory CD4+ T cells, respectively in
vitro. LSEC-expressed CXCR4 mediated CXCL12 transport and blockage of
endothelial CXCR4 inhibited CXCL12-dependent CD4+ T-cell transmigration. In
contrast, CXCR3 was not involved in the endothelial transport of its ligands
CXCL9 and CXCL10. The clathrin-specific inhibitor chlorpromazine blocked
endothelial chemokine internalization and CD4+ T-cell transmigration in vitro
as well as migration of CD4+ T cells into the inflamed liver in vivo.
Moreover, hepatic accumulation of CXCR3+ CD4+ T cells during T cell-mediated
hepatitis was strongly reduced after administration of chlorpromazine. These
data demonstrate that LSEC actively provide perivascularly expressed
homeostatic and inflammatory chemokines by CXCR4- and clathrin-dependent
intracellular transport mechanisms thereby contributing to the hepatic
recruitment of CD4+ T-cell populations during immune surveillance and liver
inflammation
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Measurements of atmospheric electricity aloft
Measurements of the electrical characteristics of the atmosphere above the surface have been made for over 200 years, from a variety of different platforms, including kites, balloons, rockets and aircraft. From these measurements, a great deal of information about the electrical characteristics of the atmosphere has been gained, assisting our understanding of the global atmospheric electric circuit, thunderstorm electrification and lightning generation mechanisms, discovery of transient luminous events above thunderstorms, and many other electrical phenomena. This paper surveys the history of atmospheric electrical measurements aloft, from the earliest manned balloon ascents to current day observations with free balloons and aircraft. Measurements of atmospheric electrical parameters in a range of meteorological conditions are described, including clear air conditions, polluted conditions, non-thunderstorm clouds, and thunderstorm clouds, spanning a range of atmospheric conditions, from fair weather, to the most electrically active