ABSTRACT
Mesenchymal stem cells (MSCs) are widely investigated as potential therapeutic agents due to their potent immunomodulatory capacity. Although specific mechanisms by which MSC acts on immune cells are emerging, many questions remain, including the potential of extracellular vesicles (EVs) to mediate biological activities. Canine MSCs are of interest for both veterinary and comparative models of disease and have been shown to suppress CD4pos T cell proliferation. The aim of this study was to determine whether EV isolated from canine Wharton's jelly-derived MSC (WJ-MSC EV) suppresses CD4pos T cell proliferation using biochemical mechanisms previously ascribed to soluble mediators [transforming growth factor beta (TGF-ß) and adenosine]. WJ-MSC EV exhibited mode of 125 nm diameter, low buoyant density (1.1 g/mL), and expression of EV proteins Alix and TSG101. Functionally, EVs inhibited CD4pos T cell proliferation in a dose-dependent manner, which was absent in EV-depleted samples and EVs from non-MSC fibroblasts. EV suppression of CD4pos T cell proliferation was inhibited by a TGF-ßRI antagonist, neutralizing antibodies to TGF-ß, or A2A adenosine receptor blockade. TGF-ß was present on EVs as latent complexes most likely tethered to EV membrane by betaglycan. These data demonstrate that canine WJ-MSC EV utilizes TGF-ß and adenosine signaling to suppress proliferation of CD4pos T cell and will enable further investigation into mechanisms of immune cell modulation, as well as refinement of WJ-MSC and their EVs for therapeutic application.
Subject(s)
Adenosine/metabolism , CD4-Positive T-Lymphocytes/physiology , Cell Proliferation , Extracellular Vesicles/metabolism , Mesenchymal Stem Cells/metabolism , Transforming Growth Factor beta/metabolism , Animals , CD4-Positive T-Lymphocytes/immunology , Calcium-Binding Proteins/metabolism , Cells, Cultured , DNA-Binding Proteins/metabolism , Dogs , Endosomal Sorting Complexes Required for Transport/metabolism , Female , Signal Transduction , Transcription Factors/metabolism , Wharton Jelly/cytologyABSTRACT
The safety of fine-needle aspiration (FNA) of the feline pancreas has not been reported. The incidence of complications following ultrasound-guided pancreatic FNA in 73 cats (pancreatic aspirate [PA] cats) with clinical and ultrasonographic evidence of pancreatic disease was compared with complications in two groups of matched control cats also diagnosed with pancreatic disease that either had abdominal organs other than the pancreas aspirated (control FNA, n = 63) or no aspirates performed (control no FNA, n = 61). The complication rate within 48 h of the ultrasound and/or aspirate procedure did not differ among the PA cats (11%), control FNA (14%) or control no FNA (8%) cats. There was no difference in rate of survival to discharge (82%, 84% and 83%, respectively) or length of hospital stay among groups. The cytologic recovery rate for the pancreatic samples was 67%. Correlation with histopathology, available in seven cases, was 86%. Pancreatic FNA in cats is a safe procedure requiring further investigation to establish diagnostic value.
Subject(s)
Biopsy, Fine-Needle/veterinary , Cat Diseases/pathology , Pancreatic Neoplasms/veterinary , Safety , Animals , Biopsy, Fine-Needle/methods , Case-Control Studies , Cats , Pancreas/pathology , Pancreatic Diseases , Pancreatic Neoplasms/pathologyABSTRACT
The disruption of prepulse inhibition (PPI) in rats by dopamine (DA) agonists is used to study the neural basis of strain differences in dopaminergic function. We reported that, compared to Long-Evans (LEH) rats, Sprague-Dawley (SDH) rats are more sensitive to the PPI-disruptive effects of the direct D1/D2 agonist apomorphine (APO) and the indirect DA agonist d-amphetamine (AMPH). This strain difference is heritable, with PPI drug sensitivity following a generational pattern (SDH>N2>F1>LEH) suggestive of additive effects of multiple genes. Here, we assessed the neurochemical bases for these heritable strain differences by measuring tissue levels of dopamine, serotonin (5HT) and their respective metabolites in several forebrain regions after vehicle, APO or AMPH administration. SDH rats were more sensitive than LEH rats to the PPI-disruptive effects of both APO (0.5 mg/kg) and AMPH (4.5 mg/kg). Several significant SDH vs. LEH strain differences in regional neurochemical levels were detected, as were drug effects on these chemicals. However, SDH, LEH and F1 rats did not exhibit differential drug sensitivity in any neurochemical indices measures. These findings suggest that inherited differences in the dopaminergic regulation of sensorimotor gating do not likely reflect differences in presynaptic forebrain dopaminergic or serotonergic processes.
Subject(s)
Dopamine Agonists/pharmacology , Dopamine/metabolism , Reflex, Startle/drug effects , Reflex, Startle/genetics , 3,4-Dihydroxyphenylacetic Acid/metabolism , Animals , Brain/drug effects , Brain/metabolism , Dopamine/genetics , Female , Male , Rats , Rats, Long-Evans , Rats, Sprague-Dawley , Species SpecificityABSTRACT
We examined American redstarts (Setophaga ruticilla) for protozoan blood parasites on their wintering grounds to determine whether transmission of these parasites occurs prior to spring migration. A total of 73 blood smears from 37 birds were examined for presence and intensity of infection. Thirty-six birds were sampled in the fall, soon after arriving from northern breeding grounds, and the spring prior to departure. Two (5%) of the samples collected in the fall were positive for Haemoproteus fringillae and one (3%) had detectable infections of Trypanosoma avium. Individuals infected with H. fringillae were hatching year redstarts sampled in September and October. Intensity of infection was 78 and < 1 infected erythrocytes per 10,000 erythrocytes, respectively. None of the birds had detectable infections when resampled prior to spring migration the following March.
