27 research outputs found
Toll-Like Receptors and Dectin-1, a C-Type Lectin Receptor, Trigger Divergent Functions in CNS Macrophages
Spinal cord injury (SCI) activates macrophages, endowing them with both reparative and pathological functions. The mechanisms responsible for these divergent functions are unknown but are likely controlled through stochastic activation of different macrophage receptor subtypes. Various danger-associated molecular patterns released from dying cells in the injured spinal cord likely activate distinct subtypes of macrophage pattern recognition receptors, including bacterial toll-like receptors (TLRs) and fungal C-type lectin receptors (e.g., dectin-1). To determine the in vivo consequences of activating these receptors, ligands specific for TLR2 or dectin-1 were microinjected, alone or in combination, into intact spinal cord. Both ligands elicit a florid macrophage reaction; however, only dectin-1 activation causes macrophage-mediated demyelination and axonal injury. Coactivating TLR2 reduced the injurious effects of dectin-1 activation. When injected into traumatically injured spinal cord, TLR2 agonists enhance the endogenous macrophage reaction while conferring neuroprotection. Indeed, dieback of axons was reduced, leading to smaller lesion volumes at the peak of the macrophage response. Moreover, the density of NG2+ cells expressing vimentin increased in and near lesions that were enriched with TLR2-activated macrophages. In dectin-1-null mutant (knock-out) mice, dieback of corticospinal tract axons also is reduced after SCI. Collectively, these data support the hypothesis that the ability of macrophages to create an axon growth-permissive microenvironment or cause neurotoxicity is receptor dependent and it may be possible to exploit this functional dichotomy to enhance CNS repair.
SIGNIFICANCE STATEMENT: There is a growing appreciation that macrophages exert diverse functions in the injured and diseased CNS. Indeed, both macrophage-mediated repair and macrophage-mediated injury occur, and often these effector functions are elicited simultaneously. Understanding the mechanisms governing the reparative and pathological properties of activated macrophages is at the forefront of neuroscience research. In this report, using in vitro and in vivo models of relevance to traumatic spinal cord injury (SCI), new data indicate that stochastic activation of toll-like and c-type lectin receptors on macrophages causes neuroprotection or neurotoxicity, respectively. Although this manuscript focuses on SCI, these two innate immune receptor subtypes are also involved in developmental processes and become activated in macrophages that respond to various neurological diseases
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On to the real world : gender and self-efficacy in Excel
Although there have been a number of studies of
end-user software development tasks, few of them have
considered gender issues for real end-user developers
in real-world environments for end-user programming.
In order to be trusted, the results of such laboratory
studies must always be re-evaluated with fewer controls,
more closely reflecting real-world conditions.
Therefore, the research question in this paper is
whether the results of a Gender HCI controlled study
generalize -- to real-world end-user developers, in a
real-world spreadsheet environment, using a realworld
spreadsheet. Our findings are that the concepts
revealed by the original laboratory study appear to be
quite robust, being demonstrated in multiple ways in
this real-world environment
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Explaining debugging strategies to end-user programmers
There has been little research into how end-user programming environments can provide explanations that could fill a critical information gap for end-user debuggers - help with debugging strategy. To address this need, we designed and prototyped a video-based approach for explaining debugging strategy, and accompanied it with a text-only approach. We then conducted a qualitative empirical study with end-user debuggers. The results reveal the influences of the explanations on end-user debuggers' decision making, how users reacted to the video versus textual media, and the information gaps the explanations closed. The results also reveal issues of particular importance to explanations of this type
History of Galaxy Interactions and their Impact on Star Formation over the Last 7 Gyr from GEMS
We perform a comprehensive estimate of the frequency of galaxy mergers and
their impact on star formation over z~0.24--0.80 (lookback time T_b~3--7 Gyr)
using 3698 (M*>=1e9 Msun) galaxies with GEMS HST, COMBO-17, and Spitzer data.
Our results are: (1) Among 790 high mass (M*>=2.5e10 Msun) galaxies, the
visually-based merger fraction over z~0.24--0.80, ranges from 9%+-5% to 8%+-2%.
Lower limits on the major and minor merger fractions over this interval range
from 1.1% to 3.5%, and 3.6% to 7.5%, respectively. This is the first
approximate empirical estimate of the frequency of minor mergers at z<1. For a
visibility timescale of ~0.5 Gyr, it follows that over T_b~3--7 Gyr, ~68% of
high mass systems have undergone a merger of mass ratio >1/10, with ~16%, 45%,
and 7% of these corresponding respectively to major, minor, and ambiguous
`major or minor' mergers. The mean merger rate is a few x 1e-4 Gyr-1 Mpc-3. (2)
We compare the empirical merger fraction and rate for high mass galaxies to a
suite of Lambda CDM-based models: halo occupation distribution models,
semi-analytic models, and hydrodynamic SPH simulations. We find qualitative
agreement between observations and models such that the (major+minor) merger
fraction or rate from different models bracket the observations, and show a
factor of five dispersion. Near-future improvements can now start to rule out
certain merger scenarios. (3) Among ~3698 M*>=1e9 Msun galaxies, we find that
the mean SFR of visibly merging systems is only modestly enhanced compared to
non-interacting galaxies over z~0.24--0.80. Visibly merging systems only
account for less than 30% of the cosmic SFR density over T_b~3--7 Gyr. This
suggests that the behavior of the cosmic SFR density over the last 7 Gyr is
predominantly shaped by non-interacting galaxies.Comment: Accepted for Publication in the Astrophysical Journal. 17 pages of
text, 21 figures, 3 tables. Uses emulateapj5.st
Irrigation Development to Improve the Lives of Impoverished Children in Kanchanaburi, Thailand
The New Life for Abused Children Project in Kanchanaburi, Thailand was established to rehabilitate underprivileged children and prepare them to reenter society. The Project is currently integrating a 32 hectare oil palm plantation into their program, but they lack a proper irrigation system. Based on environmental and social assessments of the project we designed a model system for irrigation as well as an irrigation education manual and fundraising brochure to support the system
Characterization of a new chronic lymphocytic leukemia cell line for mechanistic in vitro and in vivo studies relevant to disease.
Studies of chronic lymphocytic leukemia (CLL) have yielded substantial progress, however a lack of immortalized cell lines representative of the primary disease has hampered a full understanding of disease pathogenesis and development of new treatments. Here we describe a novel CLL cell line (OSU-CLL) generated by EBV transformation, which displays a similar cytogenetic and immunophenotype observed in the patient's CLL (CD5 positive with trisomy 12 and 19). A companion cell line was also generated from the same patient (OSU-NB). This cell line lacked typical CLL characteristics, and is likely derived from the patient's normal B cells. In vitro migration assays demonstrated that OSU-CLL exhibits migratory properties similar to primary CLL cells whereas OSU-NB has significantly reduced ability to migrate spontaneously or towards chemokine. Microarray analysis demonstrated distinct gene expression patterns in the two cell lines, including genes on chromosomes 12 and 19, which is consistent with the cytogenetic profile in this cell line. Finally, OSU-CLL was readily transplantable into NOG mice, producing uniform engraftment by three weeks with leukemic cells detectable in the peripheral blood spleen and bone marrow. These studies describe a new CLL cell line that extends currently available models to study gene function in this disease