characterization-immune-cells-proinflammatory-mediators-pulmonary

Characterization of Immune Cells and Proinflammatory Mediators in the Pulmonary Environment

Immune cell expansion, activation, and trafficking to the lungs, which are controlled by the expression of multiple cytokines and chemokines, may be ...

West Virginia University

Bryostatin, a potent protein kinase C (PKC) activator, has demonstrated therapeutic efficacy in preclinical models of associative memory, Alzheimer disease, global ischemia, and traumatic brain injury. In this study, we tested the hypothesis that administration of bryostatin provides a therapeutic benefit in reducing brain injury and improving stroke outcome using a clinically relevant model of cerebral ischemia with tissue plasminogen activator reperfusion in aged rats.

Bryostatin improves survival and reduces ischemic brain injury in aged rats after acute ischemic stroke.

Studies have indicated that pulmonary exposure to welding fumes can induce a series of adverse effects in the respiratory system, including infection, bronchitis, siderosis and decreased pulmonary function. Recent clinical and epidemiological studies have found that pulmonary exposure to welding fumes is also associated with a higher incidence of cardiovascular events. However, there is insufficient evidence to confirm a direct effect of welding fumes on the cardiovascular system. The present study investigated the effects of pulmonary exposure to welding fumes on the heart and the vascular system in rats. Two chemically distinct welding fumes generated from manual metal arc-hard surfacing (MMA-HS) and gas metal arc-mild steel (GMA-MS) welding were tested. Three groups of rats were instilled intratracheally with MMA-HS (2 mg/rat), GMA-MS (2 mg/rat) or saline as control once a week for seven weeks. On days 1 and 7 after the last treatment, basal cardiovascular function and the cardiovascular response to increasing doses of adrenoreceptor agonists were assessed. MMA-HS treatment reduced the basal levels of left ventricle end-systolic pressure and dP/dt(max) at 1 day post-treatment, and decreased dP/dt(min) in response to isoproterenol (ISO) at 7 days post-treatment. Unlike MMA-HS, GMA-MS only affected left ventricular end-diastolic pressure in response to ISO at 7 days post-treatment. Treatment with MMA-HS or GMA-MS did not alter heart rate and blood pressure. Our findings suggest that exposure to different welding fumes can induce different adverse effects on the cardiovascular system, and that cardiac contractility may be a sensitive indicator of cardiovascular dysfunction.

Cardiovascular effects in rats after intratracheal instillation of metal welding particles.

Previous studies have shown dietary cholesterol can enhance learning but retard memory which may be partly due to increased cholesterol levels in hippocampus and reduced afterhyperpolarization (AHP) amplitude of hippocampal CA1 neurons. This study explored the dose-dependent effect of dietary cholesterol on synaptic plasticity of rabbit hippocampal CA1 neurons and spine morphology, the postsynaptic structures responsible for synaptic plasticity. Field potential recordings revealed a low concentration of dietary cholesterol increased long-term potentiation (LTP) expression while high concentrations produced a pronounced reduction in LTP expression. Dietary cholesterol facilitated basal synaptic transmission but did not influence presynaptic function. DiI staining showed dietary cholesterol induced alterations in dendrite spine morphology characterized by increased mushroom spine density and decreased thin spine density, two kinds of dendritic spines that may be linked to memory consolidation and learning acquisition. Dietary cholesterol also modulated the geometric measures of mushroom spines. Therefore, dietary cholesterol dose-dependently modulated both synaptic plasticity and dendrite spine morphologies of hippocampal CA1 neurons that could mediate learning and memory changes previously seen to result from feeding a cholesterol diet.

Dietary cholesterol concentration affects synaptic plasticity and dendrite spine morphology of rabbit hippocampal neurons.

Heart rate variability (HRV) as a marker reflects the activity of the autonomic nervous system. The prognostic significance of HRV for cardiovascular disease has been reported in clinical and epidemiological studies. Our laboratory has reported alterations in rat heart rate variability (HRV) due to increasing activity of both sympathetic and parasympathetic nervous system after pulmonary exposure to multi-walled carbon nanotubes (MWCNTs). This suggests that pulmonary inhalation of engineered nanoparticles (ENs) may lead to functional changes in the cardiovascular system. The present study further investigated the effects of inhaled MWCNTs on the cardiovascular system and evaluated the correlation between the alterations in HRV and changes in cardiovascular function.

The effects of inhaled multi-walled carbon nanotubes on blood pressure and cardiac function.

Stroke-associated pneumonia (SAP) is a major cause of mortality in patients who have suffered from severe ischemic stroke. Although multifactorial in nature, stroke-induced immunosuppression plays a key role in the development of SAP. Previous studies using a murine model of transient middle cerebral artery occlusion (tMCAO) have shown that focal ischemic stroke induction results in functional defects of lymphocytes in the spleen, thymus, and peripheral blood, leading to spontaneous bacterial infection in the lungs without inoculation. However, how ischemic stroke alters immune cell niche and the expression of cytokines and chemokines in the lungs has not been fully characterized.

Ischemic stroke alters immune cell niche and chemokine profile in mice independent of spontaneous bacterial infection.

Multiple sclerosis (MS) is a chronic inflammatory disease mediated by a complex interaction between the autoreactive lymphocytes and the effector myeloid cells within the central nervous system (CNS). In a murine model of MS, experimental autoimmune encephalomyelitis (EAE), Ly6C monocytes migrate into the CNS and further differentiate into antigen-presenting cells (APCs) during disease progression. Currently, there is no information about gene signatures that can distinguish between monocytes and the monocyte-derived APCs. We developed a surface marker-based strategy to distinguish between these two cell types during the stage of EAE when the clinical symptoms were most severe, and performed transcriptome analysis to compare their gene expression. We report here that the inflammatory CNS environment substantially alters gene expression of monocytes, compared to the monocyte differentiation process within CNS. Monocytes in the CNS express genes that encode proinflammatory cytokines and chemokines, and their expression is mostly maintained when the cells differentiate. Moreover, monocyte-derived APCs express surface markers associated with both dendritic cells and macrophages, and have a significant up-regulation of genes that are critical for antigen presentation. Furthermore, we found that , and  are expressed in monocyte-derived APCs but not the Ly6C monocytes. These findings may shed light on identifying molecular signals that control monocyte differentiation and functions during EAE.

Article	Year
Bryostatin improves survival and reduces ischemic brain injury in aged rats after acute ischemic stroke. Stroke\| PubMed ID: 24172582	2013
Cardiovascular effects in rats after intratracheal instillation of metal welding particles. Inhalation toxicology\| PubMed ID: 25600139	2015
Dietary cholesterol concentration affects synaptic plasticity and dendrite spine morphology of rabbit hippocampal neurons. Brain research\| PubMed ID: 26188241	2015
The effects of inhaled multi-walled carbon nanotubes on blood pressure and cardiac function. Nanoscale research letters\| PubMed ID: 29971611	2018
Ischemic stroke alters immune cell niche and chemokine profile in mice independent of spontaneous bacterial infection. Immunity, inflammation and disease\| PubMed ID: 31691533	2019
Monocytes and Monocyte-Derived Antigen-Presenting Cells Have Distinct Gene Signatures in Experimental Model of Multiple Sclerosis. Frontiers in immunology\| PubMed ID: 31849962	2019

Wen Zheng

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