Blast cell activity in mice inflected with Hymenolepis nana, H. diminuta and Trichinella spiralis: in vivo uptake of 125IUdR in lymphoid tissues and gut

1986 ◽  
Vol 60 (4) ◽  
pp. 313-321 ◽  
Author(s):  
F. Gabriele ◽  
A. R. Ecca ◽  
D. Wakelin ◽  
C. Palmas
Keyword(s):  
Small Intestine ◽  
Trichinella Spiralis ◽  
Cell Activity ◽  
Close Correlation ◽  
Blast Cell ◽  
Lymphoid Tissues ◽  
Hymenolepis Nana ◽  
Kinetics Of ◽  
Dose Dependent

ABSTRACTThe kinetics of the lymphoblast response in mice during the course of a primary infection with Hymenolepis nana was measured by the in vivo uptake of 125IUdR. The response was most marked in tissues local to the site of infection, involving to nodes draining the small intestine but not other areas, e.g., inguinal lymph nodes. A close correlation between these responses and the course of inflection was observed. Uptake of 125IUdR was greatest in the mesenteric lymph node (MLN) but the peak reached in this organ was later than that in Peyer's patches (PP), small intestine (SI) and spleen (S). The increase in lymphoblast activity of the MLN was similar with Trichinella spiralis; no significant blast cell response to inflection with H. diminuta was found till day 9 after injection, the results being similar to those obtained when H. nana inflections were established using cysticercoids rather than eggs. It has been shown that the increase in lymphoblast activity was closely correlated with the presence of cells which are most effective in adoptive transfer immunity. A dose-dependent effect was detected in blast cell activity of MLN in different inflection levels with T. spiralis and H. nana.

In vivo changes in the intestinal reflexes and the response to CCK in the inflamed small intestine of the rat

2000 ◽  
Vol 279 (3) ◽  
pp. G543-G551 ◽  
Author(s):  
D. Torrents ◽  
P. Vergara
Keyword(s):  
Small Intestine ◽  
Motor Activity ◽  
Intestinal Inflammation ◽  
Trichinella Spiralis ◽  
Motor Responses ◽  
Morphological Alterations ◽  
Functional Changes ◽  
Residual Response ◽  
Abnormal Motor

Functional motor changes and morphological alterations have been associated with intestinal inflammation. The aim of our study was to evaluate functional alterations of intestinal reflexes and of the responses to CCK in the Trichinella spiralis model of intestinal inflammation. Rats were prepared with strain gauges and electrodes in the small intestine to evaluate spontaneous motor activity, the ascending contraction of the peristaltic reflex, and the motor responses to CCK-8 infusion. Infected animals showed increased motor activity at the duodenum and jejunum but not at the ileum. Ascending contraction was increased in both duodenum and ileum. Ascending excitation after Nω-nitro-l-arginine was still increased as well as the residual response after atropine. Response to CCK-8 during intestinal inflammation was changed in the jejunum, in which it turned from the inhibition shown in healthy animals to excitation. NADPH-diaphorase staining did not show any changes between distribution and density of positive neurons in either healthy or infected animals. In conclusion, intestinal inflammation induces functional changes in the motor activity that could explain the abnormal motor responses observed in inflammatory disorders.

The kinetics of exsheathment of infective nematode larvae is disturbed in the presence of a tannin-rich plant extract (sainfoin) both in vitro and in vivo

Parasitology ◽  
2007 ◽  
Vol 134 (9) ◽  
pp. 1253-1262 ◽  
Author(s):  
S. BRUNET ◽  
J. AUFRERE ◽  
F. El BABILI ◽  
I. FOURASTE ◽  
H. HOSTE
Keyword(s):  
Parasite Species ◽  
Gastrointestinal Nematodes ◽  
Dependent Manner ◽  
Early Step ◽  
Nematode Larvae ◽  
Kinetics Of ◽  
Dose Dependent

SUMMARYThe mode of action of bioactive plants on gastrointestinal nematodes remains obscure. Previous in vitro studies showed that exsheathment was significantly disturbed after contact with tannin-rich extracts. However, the role of important factors (extract concentration, parasite species) has not been assessed and no information is available on the occurrence in vivo. These questions represent the objectives of this study. The model incorporated the parasites Haemonchus contortus and Trichostrongylus colubriformis with sainfoin as the bioactive plant. A set of in vitro assays was performed, measuring the changes observed, after 3 h of contact with increasing concentrations of sainfoin, on the rate of artificial exsheathment. The results indicated that sainfoin extracts interfered with exsheathment in a dose-dependent manner and the process overall was similar for both nematodes. The restoration of control values observed after adding PEG to extracts confirms a major role for tannins. A second study was performed in vivo on rumen-cannulated sheep fed with different proportions of sainfoin in the diet to verify these in vitro results. The consumption of a higher proportion of sainfoin was indeed associated with significant delays in Haemonchus exsheathment. Overall, the results confirmed that interference with the early step of nematode infection might be one of the modes of action that contributes to the anthelmintic properties of tanniniferous plants.

scholarly journals T cell-mediated hepatitis in mice infected with lymphocytic choriomeningitis virus. Liver cell destruction by H-2 class I-restricted virus-specific cytotoxic T cells as a physiological correlate of the 51Cr-release assay?

1986 ◽  
Vol 164 (4) ◽  
pp. 1075-1092 ◽  
Author(s):  
R M Zinkernagel ◽  
E Haenseler ◽  
T Leist ◽  
A Cerny ◽  
H Hengartner ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Adoptive Transfer ◽  
Cytotoxic T Cells ◽  
Lymphocytic Choriomeningitis ◽  
Cytotoxic T Cell ◽  
Release Assay ◽  
Kinetics Of ◽  
Dose Dependent

A model for immunologically T cell-mediated hepatitis was established in mice infected with lymphocytic choriomeningitis virus (LCMV). The severity of hepatitis was monitored histologically and by determination of changes in serum levels of the enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH), and alkaline phosphatase (AP). Kinetics of histological disease manifestations, increases of liver enzyme levels in the serum, and cytotoxic T cell activities in livers and spleens all correlated and were dependent upon several parameters: LCMV-isolate; LCMV-WE caused extensive hepatitis, LCMV-Armstrong virtually none. Virus dose. Route of infection; i.v. or i.p. infection caused hepatitis, whereas infection into the footpad did not. The general genetic background of the murine host; of the strains tested, Swiss mice and A-strain mice were more susceptible than C57BL or CBA mice; BALB/c and DBA/2 mice were least susceptible. The degree of immunocompetence of the murine host; T cell deficient nu/nu mice never developed hepatitis, whereas nu/+ or +/+ mice always did. B cell-depleted anti-IgM-treated mice developed immune-mediated hepatitis comparably or even more extensively than control mice. Local cytotoxic T cell activity; mononuclear cells isolated from livers during the period of overt hepatitis were two to five times more active than equal numbers of spleen cells. Adoptive transfer of nylon wool-nonadherent anti-Thy-1.2 and anti-Lyt-2 plus C-sensitive, anti-L3T4 plus C-resistant lymphocytes into irradiated mice preinfected with LCMV-WE caused a rapid time- and dose-dependent linear increase of serum enzyme levels. This increase was caused by adoptive transfer of lymphocytes if immune cell donors and recipient mice shared class I, but not when they shared class II histocompatibility antigens. The donor cell dose-dependent increase of these enzymes was first measurable 6-18 h after transfer with 2 X 10(8) cells or 3 X 10(6) cells, respectively. The time-dependent increase caused by the adoptive transfer of 1-2 X 10(8) cells was strictly linear during a period of up to 25-40 h. These results indicate single-hit kinetics of liver cell death and suggest that effector T cells destroy infected liver cells via direct contact rather than via soluble toxic mediators. The results may represent the best in vivo correlate of the in vitro 51Cr-release assay that has been analyzed so far, and strongly support the view that antiviral cytotoxic T cells are directly cytolytic in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Preferential Small Intestine Homing and Persistence of CD8 T Cells in Rhesus Macaques Achieved by Molecularly Engineered Expression of CCR9 and Reduced Ex Vivo Manipulation

2019 ◽  
Vol 93 (21) ◽  
Author(s):  
Matthew T. Trivett ◽  
James D. Burke ◽  
Claire Deleage ◽  
Lori V. Coren ◽  
Brenna J. Hill ◽  
...  
Keyword(s):  
T Cells ◽  
Small Intestine ◽  
T Cell ◽  
Rhesus Macaque ◽  
Cd8 T Cells ◽  
Ex Vivo ◽  
Rhesus Macaques ◽  
Lymphoid Tissues ◽  
Aids Virus

ABSTRACT Adoptive cell transfer (ACT) is a powerful experimental approach to directly study T-cell-mediated immunity in vivo. In the rhesus macaque AIDS virus model, infusing simian immunodeficiency virus (SIV)-infected animals with CD8 T cells engineered to express anti-SIV T-cell receptor specificities enables direct experimentation to better understand antiviral T-cell immunity in vivo. Limiting factors in ACT experiments include suboptimal trafficking to, and poor persistence in, the secondary lymphoid tissues targeted by AIDS viruses. Previously, we redirected CD8 T cells to B-cell follicles by ectopic expression of the CXCR5 homing protein. Here, we modify peripheral blood mononuclear cell (PBMC)-derived CD8 T cells to express the CCR9 chemokine receptor, which induces preferential homing of the engineered cells to the small intestine, a site of intense early AIDS virus replication and pathology in rhesus macaques. Additionally, we increase in vivo persistence and overall systemic distribution of infused CD8 T cells, especially in secondary lymphoid tissues, by minimizing ex vivo culture/manipulation, thereby avoiding the loss of CD28+/CD95+ central memory T cells by differentiation in culture. These proof-of-principle results establish the feasibility of preferentially localizing PBMC-derived CD8 T cells to the small intestine and enables the direct experimental ACT-based assessment of the potential role of the quality and timing of effective antiviral CD8 T-cell responses to inhibit viral infection and subsequent replication in small intestine CD4 T cells. More broadly, these results support the engineered expression of homing proteins to direct CD8 T cells to target tissues as a means for both experimental and potential therapeutic advances in T-cell immunotherapies, including cancer. IMPORTANCE Adoptive cell transfer (ACT) of T cells engineered with antigen-specific effector properties can deliver targeted immune responses against malignancies and infectious diseases. Current T-cell-based therapeutic ACT relies on circulatory distribution to deliver engineered T cells to their targets, an approach which has proven effective for some leukemias but provided only limited efficacy against solid tumors. Here, engineered expression of the CCR9 homing receptor redirected CD8 T cells to the small intestine in rhesus macaque ACT experiments. Targeted homing of engineered T-cell immunotherapies holds promise to increase the effectiveness of adoptively transferred cells in both experimental and clinical settings.

Absorption of Galactose by the Rat Small Intestine in Vivo: Proximal—Distal Kinetic Gradients and a New Method to Express Absorption Per Enterocyte

1976 ◽  
Vol 50 (6) ◽  
pp. 499-509 ◽  
Author(s):  
R. M. Batt ◽  
T. J. Peters
Keyword(s):  
Small Intestine ◽  
Absorptive Capacity ◽  
Proximal Jejunum ◽  
Rat Small Intestine ◽  
Experimental Conditions ◽  
Carrier Mediated Transport ◽  
Saturation Kinetics ◽  
Kinetics Of ◽  
Diffusive Component

1. The absorption in vivo of d-galactose by the rat small intestine has been examined in proximal jejunum and distal ileum by use of a recirculation—perfusion technique. 2. Multiple sequential perfusions over 4 h produced no subsequent functional or morphological damage in the perfused segments. 3. Absorption of galactose from 8 and 64 mmol/l solutions was found to be independent of flow rate over the range 1·0–6·5 ml/min. 4. Galactose absorption in both the jejunum and the ileum exhibited saturation kinetics of the Michaelis—Menten type, and phlorrhizin sensitivity. Sorbose was only absorbed minimally. These observations demonstrate that galactose is absorbed by carrier-mediated transport and that there is no significant passive diffusive component in vivo. 5. Under the stated experimental conditions, the maximum absorptive capacity was 4·5 times greater in the jejunum than in the ileum. The Michaelis constant for galactose was higher in the jejunum than in the ileum. 6. Enterocytes were isolated from perfused segments and quantified by DNA assay with a correction for yield. In this manner, the absorptive capacity per enterocyte was calculated. 7. The maximum absorptive capacity per enterocyte was 3·5 times greater in the jejunum than in the ileum.

scholarly journals REGULATORY MECHANISMS IN CELL-MEDIATED IMMUNE RESPONSES

1974 ◽  
Vol 140 (6) ◽  
pp. 1588-1603 ◽  
Author(s):  
Susan Solliday Rich ◽  
Robert R. Rich
Keyword(s):  
Lymph Node ◽  
Regional Lymph Node ◽  
Cell Activity ◽  
Suppressor Cell ◽  
Spleen Cells ◽  
Cytotoxic Effects ◽  
Lymph Node Cells ◽  
Regulatory Effects ◽  
Kinetics Of

Regulatory effects of alloantigen-activated thymus-derived lymphocytes in mixed lymphocyte reactions have been demonstrated. Mice were injected into foot pads with allogeneic spleen cells; 4 days following sensitization spleen or regional lymph node cells from these animals were treated with mitomycin C and incorporated into MLR as regulator populations syngeneic to the responder cell type. Activated spleen cells suppressed MLR responses 60–90% whereas activated lymph node cells from the same animals enhanced MLR responses. Suppression by activated spleen cells was not due to cytotoxic effects nor to altered kinetics of the proliferative response. Studies of splenic suppressor cell generation in vivo revealed peak activity four days after alloantigen stimulation with no activity demonstrable at 7 days or at later times. Suppressor cell activity was abrogated by treatment with anti-θC3H serum and complement, and was not alloantigen specific.

scholarly journals Magnolia officinalisExtract Contains Potent Inhibitors against PTP1B and Attenuates Hyperglycemia in db/db Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Jing Sun ◽  
Yongsen Wang ◽  
Xueqi Fu ◽  
Yingli Chen ◽  
Deli Wang ◽  
...  
Keyword(s):  
Tyrosine Phosphatase ◽  
C2c12 Myotubes ◽  
Dependent Manner ◽  
Inhibitory Potential ◽  
Magnolia Officinalis ◽  
Kinetics Of ◽  
Dose Dependent

Protein tyrosine phosphatase 1B (PTP1B) is an established therapeutic target for type 2 diabetes mellitus (T2DM) and obesity. The aim of this study was to investigate the inhibitory activity ofMagnolia officinalisextract (ME) on PTP1B and its anti-T2DM effects. Inhibition assays and inhibition kinetics of ME were performedin vitro. 3T3-L1 adipocytes and C2C12 myotubes were stimulated with ME to explore its bioavailability in cell level. Thein vivostudies were performed on db/db mice to probe its anti-T2DM effects. In the present study, ME inhibited PTP1B in a reversible competitive manner and displayed good selectivity against PTPsin vitro. Furthermore, ME enhanced tyrosine phosphorylation levels of cellular proteins, especially the insulin-induced tyrosine phosphorylations of insulin receptorβ-subunit (IRβ) and ERK1/2 in a dose-dependent manner in stimulated 3T3-L1 adipocytes and C2C12 myotubes. Meanwhile, ME enhanced insulin-stimulated GLUT4 translocation. More importantly, there was a significant decrease in fasting plasma glucose level of db/db diabetic mice treated orally with 0.5 g/kg ME for 4 weeks. These findings indicated that improvement of insulin sensitivity and hypoglycemic effects of ME may be attributed to the inhibition of PTP1B. Thereby, we pioneered the inhibitory potential of ME targeted on PTP1B as anti-T2DM drug discovery.

scholarly journals Abl family tyrosine kinases govern IgG extravasation in the skin in a murine pemphigus model

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Sachiko Ono ◽  
Gyohei Egawa ◽  
Takashi Nomura ◽  
Akihiko Kitoh ◽  
Teruki Dainichi ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Kinase Inhibitor ◽  
Dependent Manner ◽  
Endocytic Vesicle ◽  
Fcγ Receptors ◽  
Pathological Mechanism ◽  
Endocytic Vesicles ◽  
Kinetics Of ◽  
Dose Dependent

Abstract The pathway of homeostatic IgG extravasation is not fully understood, in spite of its importance for the maintenance of host immunity, the management of autoantibody-mediated disorders, and the use of antibody-based biologics. Here we show in a murine model of pemphigus, a prototypic cutaneous autoantibody-mediated disorder, that blood-circulating IgG extravasates into the skin in a time- and dose-dependent manner under homeostatic conditions. This IgG extravasation is unaffected by depletion of Fcγ receptors, but is largely attenuated by specific ablation of dynamin-dependent endocytic vesicle formation in blood endothelial cells (BECs). Among dynamin-dependent endocytic vesicles, IgG co-localizes well with caveolae in cultured BECs. An Abl family tyrosine kinase inhibitor imatinib, which reduces caveolae-mediated endocytosis, impairs IgG extravasation in the skin and attenuates the murine pemphigus manifestations. Our study highlights the kinetics of IgG extravasation in vivo, which might be a clue to understand the pathological mechanism of autoantibody-mediated autoimmune disorders.

scholarly journals Macrophages as origin of factor increasing monocytopoiesis.

1987 ◽  
Vol 166 (4) ◽  
pp. 909-922 ◽  
Author(s):  
W Sluiter ◽  
E Hulsing-Hesselink ◽  
I Elzenga-Claasen ◽  
L W van Hemsbergen-Oomens ◽  
A van der Voort van der Kleij-van Andel ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cell Lineage ◽  
Blood Monocytes ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Bone Marrow Macrophage ◽  
Kinetics Of ◽  
Dose Dependent

Earlier investigations had indicated that the factor increasing monocytopoiesis (FIM), present in the serum of mice and rabbits during the onset of an inflammatory response, is released by cells of the inflammatory exudate. The present study was performed to determine which cells produce and secrete this factor and to establish the kinetics of its production and secretion. FIM was assayed in vivo by intravenous injection of samples into untreated mice and monitoring the course of the number of blood monocytes in the recipients. FIM was assayed in vitro by adding samples to cultures of the macrophage cell line PU5 and determining the rate of proliferation of the cells. The results show that only macrophages contain and synthesize FIM. This factor is secreted upon exposure to a phagocytic stimulus, and after the release of preformed FIM, macrophages secrete newly synthesized FIM. Granulocytes and lymphocytes neither contain nor secrete FIM. The characteristics of FIM derived from macrophages are in all aspects similar to those of FIM in serum. Macrophage-derived FIM is a protein with a molecular weight between 10 and 25 X 10(3), its activity is cell-lineage specific and dose dependent, and it stimulates monocyte production in the bone marrow. Macrophage-derived FIM is not identical to either CSF-1 or IL-1, and has no chemotactic activity. Taken together, the present results show that FIM occurring in serum during an inflammatory response originates from macrophages at the site of the inflammation. In this way the macrophages themselves regulate the supply of circulating blood monocytes that can migrate to the site of injury when needed.

Biological variation in Trichinella species and genotypes

2003 ◽  
Vol 77 (2) ◽  
pp. 111-118 ◽  
Author(s):  
F. Bolas-Fernández
Keyword(s):  
Host Response ◽  
Inflammatory Responses ◽  
Trichinella Spiralis ◽  
Biological Significance ◽  
Heterologous Challenge ◽  
Diagnostic Characteristics ◽  
Muscle Larvae ◽  
Specific Antigens ◽  
Kinetics Of ◽  
Dose Dependent

AbstractAt present, the genus Trichinella comprises seven species of which five have encapsulated muscle larvae (T. spiralis, T. nativa, T. britovi, T. nelsoni and T. murrelli) and two do not (T. pseudospiralis and T. papuae) plus three genotypes of non-specific status (T6, T8 and T9). The diagnostic characteristics of these species are based on biological, biochemical and genetic criteria. Of biological significance is variation observed among species and isolates in parameters such as infectivity and immunogenicity. Infectivity of Trichinella species or isolates is determined, among other considerations, by the immune status of the host in response to species- or isolate-specific antigens. Common and particular antigens determine the extent of protective responses against homologous or heterologous challenge. The kinetics of isotype, cytokine and inflammatory responses against T. spiralis infections are isolate-dependent. Trichinella spiralis and T. pseudospiralis induce different dose-dependent T-cell polarizations in the early host response, with T. spiralis initially preferentially promoting Th1-type responses before switching to Th2 and T. pseudospiralis driving Th2-type responses from the outset.

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