scholarly journals Ineffective delivery of diet-derived microRNAs to recipient animal organisms

RNA Biology ◽  
2013 ◽  
Vol 10 (7) ◽  
pp. 1107-1116 ◽  
Author(s):  
Jonathan W. Snow ◽  
Andrew E. Hale ◽  
Stephanie K. Isaacs ◽  
Aaron L. Baggish ◽  
Stephen Y. Chan
Keyword(s):  
Recipient Animal

Insights Into Thrombopoiesis From Infused Human Megakaryocytes Into Mice

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1165-1165
Author(s):  
Yuhuan Wang ◽  
Vincent M. Hayes ◽  
Prasuna Paluru ◽  
Stella T. Chou ◽  
Deborah L. French ◽  
...  
Keyword(s):  
Half Life ◽  
Size Range ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Human Donor ◽  
Nsg Mice ◽  
Infusion Study ◽  
Recipient Animal ◽  
Post Infusion

Abstract Thrombopoiesis is the process by which megakaryocytes (Megs) release platelets (Plts), but issues remain as to the detailed in vivo mechanisms underlying this process. We now report new insights into this process by studying infused human Megs into immunocompromized NOD/SCID, gamma-interferon deleted (NSG) mice. Prior in situ microscopy has suggested that Megs release varied-size cytoplasmic fragments up to whole Megs in size into the medullary vascular space. Other studies have suggested that at least a portion of thrombopoiesis occurs by Megs lodged in the lungs. We previously infused ex vivo-generated murine Megs into mice and found that these Megs become entrapped in the animals’ lungs, and in <1.5 hrs, release functional Plts (termed here “Meg-Plts”) that have a similar half-life as infused mouse donor-derived Plts (termed here “Donor-Plts”). To better understand the biology of thrombopoiesis, we have infused ex vivo-generated human Megs into NSG mice. These studies replicated many of the observations seen with infused murine Megs: Human Megs were entrapped in the lungs with delayed release of human Meg-Plts, and these Meg-Plts had the same half-life as infused human Donor-Plts. Human Plts differ from murine Plts in size so this parameter was analyzed following infusion of human Megs using forward cell scatter analysis. We noted that 10 mins post-infusion, the Meg-Plt size range was wide and displayed a non-bell-shaped distribution. This distribution was in contrast to the tight bell-shaped curves seen for the endogenous murine Plts and for infused human Donor-Plts. However, by 3 hrs post-human Meg infusion - at the time of peak Meg-Plt counts - the human Meg-Plts now displayed an identical bell-shaped distribution curve as infused human Donor-Plt. The smaller, human Meg-Plts had disappeared. The size and distribution of these Meg-Plts then remained near identical to Donor-Plts for the remaining portion of the 48 hr post-infusion study. However, after impairing macrophage clearance in NSG recipient mice with clodronate-ladened liposome infusion, the small Meg-Plts did not disappear and were present at 48 hrs. Using thiazole orange (TO) to stain platelets for RNA content, we noted that ∼70% of all Meg-Plts were initially TO+ compared to the steady-state of ∼10% for mouse endogenous platelets. This high TO+ state decreased to near 10% by 24 hrs post-infusion. Up to ∼6 hrs, all of the large Meg-Plts were TO+, while the smaller-sized Meg-Plts were predominantly TO-. Unless the mice were treated with clodronate-ladened liposomes, these TO-, small Meg-Plts disappeared before 6 hrs. In conclusion, these data support that ex vivo-generated human Megs release physiologic platelets in the pulmonary vascular bed of NSG mice with the same size range/distribution and survival as infused human Donor-Plts. Mean Meg-Plt size depends on the species of origin of the infused Megs rather than on the species of the recipient animal. We did not detect large Meg cytoplasmic fragments that underwent further size reduction although our technique may not be capable of detecting small numbers of such fragments or the small size changes that would accompany platelet maturation from preplatelets. Our data also suggest that Megs generated in culture release a wide size range of non-physiologic Plt-like particles that when infused are cleared rapidly by macrophages. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Activation of macrophages for enhanced release of superoxide anion and greater killing of Candida albicans by injection of muramyl dipeptide.

1980 ◽  
Vol 152 (6) ◽  
pp. 1659-1669 ◽  
Author(s):  
N P Cummings ◽  
M J Pabst ◽  
R B Johnston
Keyword(s):  
Candida Albicans ◽  
Superoxide Anion ◽  
Specific Activity ◽  
Muramyl Dipeptide ◽  
Peritoneal Macrophages ◽  
Cell Protein ◽  
Bacillus Calmette Guerin ◽  
Myristate Acetate ◽  
Recipient Animal

The adjuvant muramyl dipeptide (MDP) has been shown to affect a number of macrophage functions in vitro. We studied the effect of subcutaneous injection of MDP into mice. Cultured peritoneal macrophages from treated mice displayed increased spreading, total cell protein, and specific activity of beta-glucosaminidase a constituent of macrophage lysosomes, and of lactate dehydrogenase. Generation of superoxide anion (O2-) by MDP-treated macrophages stimulated by contact with phorbol myristate acetate was enhanced by over fivefold to levels achieved by macrophages from bacillus Calmette-Guérin-infected mice. The enhancement in stimulated O2- release was noted by 1 h after injection of MDP, peaked by 3 h, and remained high for at least 48 h. Priming for enhancement of O2- release by MDP was similar in athymic nude mice and in normal littermates, suggesting that mature T lymphocytes are not involved in this MDP effect. Priming for enhanced stimulated O2- release, and morphologic and enzymic changes, were not achieved by injection of the D-D stereoisomer of MDP. Phagocytosis of Candida albicans was only slightly greater by macrophages from mice give MDP, but MDP-stimulated cells killed two times more C. albicans in vitro than did cells from untreated animals. When MDP was given 18 h before, simultaneously with, or 24 h after lethal infectious challenge with C. albicans, treated mice were protected compared with controls. These results suggest that injection of MDP effectively and rapidly activates macrophages in the recipient animal. This agent should serve as an important probe of macrophage physiology and, perhaps ultimately, as a means of enhancing host defense in humans.

scholarly journals CELLS INVOLVED IN THE IMMUNE RESPONSE

1969 ◽  
Vol 129 (6) ◽  
pp. 1261-1273 ◽  
Author(s):  
M. Richter ◽  
N. I. Abdou
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Plaque Formation ◽  
Lymphoid Cells ◽  
Spleen Cells ◽  
Normal Bone ◽  
Large Numbers ◽  
Recipient Animal ◽  
Rabbit Bone ◽  
Marrow Cells

Bone marrow cells obtained from rabbits of one allotype were injected into irradiated rabbits of a different allotype. The recipients were also injected with sheep red blood cells, and their spleen cells were tested for plaque-forming capacity 7 days later. Spleen cells of all recipients gave large numbers of plaques as did spleen cells incubated with antiserum, directed toward donor allotype. However, incubation of the recipient spleen cells with antiserum directed toward recipient allotype completely suppressed plaque formation. These results demonstrate that antibody-formation in irradiated recipients of transferred lymphoid cells is a property of the recipient animal and that the antibody-forming cell is relatively irradiation-resistant. It was also demonstrated that only viable normal bone marrow cells are capable of transferring antibody-forming capacity to irradiated recipient rabbits. Neither sonicates nor heat-killed preparations of normal rabbit bone marrow cells possessed this capacity.

Host-parasite relationship of Angiostrongylus cantonensis 1. Intracranial transplantation into various hosts

1979 ◽  
Vol 53 (2) ◽  
pp. 121-126 ◽  
Author(s):  
Ronald C. Ko
Keyword(s):  
Growth Rate ◽  
Angiostrongylus Cantonensis ◽  
Initial Growth ◽  
Fourth Stage ◽  
Host Parasite Relationship ◽  
Parasite Relationship ◽  
Recipient Animal ◽  
Host Parasite ◽  
Relationship Of ◽  
The Brain

ABSTRACTVarious stages of Angiostrongylus cantonensis recovered from the brain of experimentally infected mice were transplanted intracranially into rats. Third and fourth-stage worms recovered 2–7 days postinfection were able to develop normally after transplantation into recipient rats. The fifth-stage worm obtained 14–15 days postinfection would enter the brain tissue of rats but died shortly afterwards. However, the same stage of worms recovered from rats, after a similar transplantation, were found to develop normally in the recipient animal. Young fifth-stage worms, from the subarachnoid space of rats, which were ready for the pulmonary migration were also transplanted into rabbits but the worms failed to reach the lungs. In the control rat-to-rat transplantation, the worms successfully completed the pulmonary migration. The morphogenesis and initial growth rate of A. cantonensis were similar in both mice and rats but in the former host the worms started to grow at a markedly slower rate after the last moult and gradually degenerated.

scholarly journals Sensory neurons expressing the atypical olfactory receptor guanylyl cyclase D are required for the acquisition of odor preferences by mice in diverse social contexts

2020 ◽  
Author(s):  
Arthur D. Zimmerman ◽  
Christina R. Nagy ◽  
Steven D. Munger
Keyword(s):  
Sensory Neurons ◽  
Guanylyl Cyclase ◽  
Olfactory Receptor ◽  
Food Preferences ◽  
Conditioned Aversion ◽  
Social Contexts ◽  
Social Investigation ◽  
The Social ◽  
Recipient Animal ◽  
Odor Preferences

ABSTRACTAnimals use social communication to learn important information from conspecifics that can guide appropriate behavioral choices. For example, during the social transmission of food preference (STFP), conspecific semiochemicals detected by mouse olfactory sensory neurons (OSNs) expressing the atypical olfactory receptor guanylyl cyclase D (GC-D+ OSNs) promote the acquisition of food preferences in the recipient animal, mitigating the risk of ingesting food contaminated with toxins or pathogens. However, it is unclear if GC-D+ OSNs mediate preference learning outside this specific context. Here, we report that GC-D+ OSNs are required for the acquisition of odor preferences by both adult and juvenile mice, and that GC-D-dependent preference could be formed for conditionally aversive odors. We used a two-choice olfactory behavioral test to assess odor preferences in adult Gucy2d +/+, +/- and -/- mice that encountered novel odors together with GC-D+ OSN stimuli (guanylin family peptides), during social investigation of a live conspecific, or during suckling as pups. Gucy2d +/+ and +/-mice (which express functional GC-D), but not Gucy2d -/- littermates, successfully acquire a preference for the demonstrated odor in any of these behavioral paradigms. Mice could even acquire a GC-D-dependent preference for odors to which they had recently formed a conditioned aversion. Together, these results demonstrate that GC-D+ OSNs mediate the acquisition of socially-transmitted odor preferences in different social and experiential contexts and at different life stages.

scholarly journals Polypeptide Secretion from the Isolated Parietovisceral Ganglion of Aplysia californica

1972 ◽  
Vol 59 (1) ◽  
pp. 47-59 ◽  
Author(s):  
S. Arch
Keyword(s):  
Polyacrylamide Gel Electrophoresis ◽  
Aplysia Californica ◽  
Sodium Dodecyl ◽  
Egg Laying ◽  
High Potassium ◽  
Bathing Medium ◽  
Initial Exposure ◽  
Recipient Animal ◽  
Bag Cells

In vitro studies of the secretory behavior of the parietovisceral ganglion in Aplysia californica were performed. The aim of these studies was to investigate the release of polypeptides in response to depolarizing stimuli, and, in particular, to determine if a specific polypeptide known to induce egg laying in the intact animal is secreted into the bathing medium. During continuous perfusion of a ganglion preincubated in leucine-3H the application of either high-potassium medium or a burst of electrical stimuli (via the pleurovisceral connective nerve) evoked a marked increase in the amount of trichloroacetic acid (TCA)-precipitable radioactivity recovered in the perfusate. Enhanced release could be detected within 80 sec of the initial exposure to high potassium; however, incubation of a ganglion in calcium-free media before the application of high-potassium medium abolished the increase of precipitable radioactivity. Sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis of perfusate samples revealed a significant change in the polypeptide species washed from the ganglion during high-potassium depolarization. Bioassays confirmed that egg laying is induced when high-potassium medium used to bathe a ganglion is injected into a recipient animal. These and other results permit the conclusion that the bulk of the polypeptide material secreted from the ganglion in response to depolarization is a specific neurohormone produced by two identified cell clusters, the so-called bag cells.

scholarly journals Heterotopic uterine transplantation by vascular anastomosis in the mouse

2002 ◽  
Vol 174 (2) ◽  
pp. 157-166 ◽  
Author(s):  
R Racho El-Akouri ◽  
G Kurlberg ◽  
G Dindelegan ◽  
J Molne ◽  
A Wallin ◽  
...  
Keyword(s):  
Blood Flow ◽  
Vena Cava ◽  
Vascular Supply ◽  
Uterine Horn ◽  
Vascular Anastomosis ◽  
F1 Hybrids ◽  
Donor Animal ◽  
Uterine Transplantation ◽  
Recipient Animal ◽  
The Right

A method of heterotopic uterine transplantation was developed in the mouse as a model system for studies of uterine function and transplant immunology of the uterus. The model involved transplantation of the right uterine horn and the cervix by vascular anastomosis to a donor animal with the intact native uterus remaining in situ. F1-hybrids of inbred C57BL/6 x CBA/ca (B6 CBAF1) mice of 6-8 weeks of age (n=42) were used. The specific pelvic vascular anatomy of these mice was first examined by intra-aortal injection of a two-component silicon-rubber curing agent. The surgery of the donor animal involved microsurgical isolation of the right uterine horn and the cervix, with preserved vascular supply from the aorta through the right uterine artery. After isolation of the uterine horn with vascular supply and venous drainage, including approximately 3 mm of the inferior vena cava and aorta, the organ was put on ice. The recipient animal was prepared by exposing and mobilizing the infrarenal part of the aorta and the vena cava. The grafted uterus was placed in the abdomen on the left side and the aorta and vena cava of the graft were anastomosed end-to-side to the aorta and vena cava of the recipient animal with 11-0 sutures. The total time for these procedures declined with time and was 125+/-4 min for the last 28 operations. Viability of the uterus was confirmed, several days later, by demonstrating a blood flow similar to that of the native uterus, and histology of the grafted uterus demonstrated normal morphology, including intact ultrastructure of the endothelial cells. The overall survival rate of the recipient animals increased with learning from approximately 40% in animals 1-21 to 71% in animals 22-42. The proportion of viable grafts, as judged by normal blood flow and histology among the surviving mice was 25% in animals 1-21 and 87% in animals 22-42. An undisturbed function of the transplanted uterus horn was finally demonstrated by its ability to implant inserted blastocysts and to carry pregnancy with fetal weight being similar to that of fetuses in the native uterus and controls. In conclusion, this is the first report of successful transplantation of the uterus with proven functionality in the mouse. The model should be useful for many aspects of research in uterine physiology and pathophysiology.

scholarly journals Antigen- and receptor-driven regulatorymechanisms. The failure of idiotype- coupled spleen cells to induce unresponsiveness in animals lacking the appropriate VH genes is caused by the lack of idiotype-matehed targets

1980 ◽  
Vol 152 (5) ◽  
pp. 1226-1235 ◽  
Author(s):  
M-S Sy ◽  
MH Dietz ◽  
A Nisonoff ◽  
RN Germain ◽  
B Benacerraf ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Function ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Spleen Cells ◽  
Suppressor T Cell ◽  
Recipient Animal ◽  
Vh Genes ◽  
In Vitro Treatment

A/J anti-p-azobenzenearsonate (ABA) antibodies bearing cross-reactive idiotypic (CRI) determinants, when coupled to spleen cells and then injected intravenously into naive animals, stimulate suppressor T cell (Ts) responses. Moreover, previous studies have demonstrated that the ability of such idiotype-coupled spleen cells to induce immune unresponsiveness to subsequent immunization with ABA-coupled spleen cells is linked to Igh-1 genes. Thus, CRI bearing antibodies from A/J mice, when conjugated to normal BALB/c spleen cells in vitro and then injected intravenously to syngeneic BALB/c mice, failed to induce tolerance in these animals. However, spleen cells taken from these animals transferred significant degrees of suppression to Igh-1 congenic C.AL-20 but not to H-2 congenic, Igh-1 distinct B10.D2 mice. Therefore, the failure of CRI-coupled spleen cells to induce suppressor cell- mediated unresponsiveness in animals unable to express the appropriate VH genes (i.e. BALB/c and B10.D2) appears to be caused by the lack of idiotype- matched targets. The notion that the ability to express certain Vn genes in the recipient animal is a prerequisite for suppressor cell function was further supported by the observation that suppressor cells induced in C.AL-20 mice failed to transfer any degree of suppression to BALB/c mice. The ability to transfer suppression from BALB/c mice to C.AL-20 mice is a T cell- dependent phenomenon, since in vitro treatment with anti-Thy 1.2 antiserum and complement completely abrogated suppressor cell function. Furthermore, these suppressor T cells are antigen specific and can be enriched on idiotype-coated petri dishes, indicating they possess anti-idiotypic receptors. Therefore, appropriate anti-idiotype and idiotype interaction is essential for the manifestation of suppressor T cell function in ABA-specific suppressor pathways.

Shortening of Platelet Survival by Induced Hypercholesterolaemia In Rabbits and Its Prolongation by Anagrelide

1983 ◽  
Vol 50 (03) ◽  
pp. 656-659 ◽  
Author(s):  
P A Barrett ◽  
K D Butler
Keyword(s):  
Arachidonic Acid ◽  
Half Life ◽  
Functional Change ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Male And Female ◽  
Platelet Survival ◽  
Recipient Animal ◽  
Increased Sensitivity

SummaryInduction of atherosclerosis in rabbits by feeding a cholesterol enriched diet reduced the platelet half-life in male rabbits from 37.0 ± 4.1 hr to 30.1 ± 3.9 hr (mean ± S.D. p ≤0.01). Platelets from these animals exhibited increased sensitivity to arachidonic acid but decreased sensitivity to ADP. No significant change was found in aggregation to collagen or thrombin, or in the production of thomboxane B2 induced by collagen.The reduced platelet survival was dependent upon the recipient animal and not the platelet donor. Platelets from cholesterol- fed animals survived normally in normal animals, whereas platelets from normal animals in cholesterol-fed animals had a reduced platelet survival even compared to platelets from cholesterol-fed animals. This might suggest that some functional change had occurred in the cholesterol platelet in response to its altered environment.Anagrelide (1 mg/kg/day) normalised shortened platelet survival in both male and female rabbits fed the high cholesterol diet.

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