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At least 145 records · Page 8Linked to original sources
PubMed2004

Oestrous cycle-regulated expression of inositol 1,4,5-trisphosphate receptor type 2 in the pig ovary.

The inositol 1,4,5-trisphosphate receptor type 2 (IP(3)R-2) is an intracellular Ca(2+) release channel responsible for mobilizing of Ca(2+) from intracellular storage sites and plays a key role in biological processes such as fertilization, cell differentiation, and growth. To study the cell-type-specific IP(3)R-2 expression in porcine ovaries during different phases of the oestrous cycle, we used reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. A total of 24 ovaries from gilts were collected in early luteal, mid-luteal, and follicular phases of the oestrous cycle. When amplified with the primers common to IP(3)R-2, a RT-PCR product of the expected size (approximately 388 bp) was clearly detected in the follicular and early luteal phase of the oestrous cycle, but there was no detectable PCR product in the corpus luteum of the mid-luteal phase of the oestrous cycle. Immunohistochemical studies showed that IP(3)R-2 protein is expressed in granulosa cells and theca cells of growing follicles. IP(3)R-2 immunostaining was first detected during the late pre-antral stage in granulosa and theca cells. Granulosa cell IP(3)R-2 expression increased from the pre-antral to mid-antral stage, but was strongly reduced in pre-ovulatory follicles. In the developing corpus luteum, intense IP(3)R-2 immunostaining was also present in luteal cells, but undetectable in mid-luteal corpora lutea. Furthermore, oocytes, atretic follicles and regressed corpora lutea were negative for IP(3)R-2. Our results indicate that the expression of the IP(3)R-2 protein was downregulated in terminally differentiated granulosa cells of pre-ovulatory follicles when granulosa cells lose follicle-stimulating hormone responsiveness. Therefore, we strongly suggest that IP(3)R-2 may play an important role in the initiation and propagation of intracellular Ca(2+) signals during follicular development of the pig.

Animals↗
PubMed1993

Stimulation of phosphoinositides by agents that stimulate proton secretion in toad urinary bladder.

The urinary bladder of Bufo marinus excretes H+ and this excretion is increased by metabolic acidosis (MA), insulin (IN), prostaglandin E2 (PGE2), increases CO2, and aldosterone. The purpose of this experiment was to determine whether MA, IN, PGE2, CO2, and aldosterone stimulate inositol phosphate's (IP) formation in isolated cells of toad urinary bladder. Cells were prepared by treating bladder sacs with collagenase. Cells were obtained from 10 toads in MA and 10 normal toads, suspended in 2 ml of Ringer's solution containing LiCl (10 mM), myo-inositol (5 mM), and [3H]myo-inositol (10 microCi), and then incubated for 2 hr at 25 degrees C. Cells were homogenized and the IP fractions quantitated by column chromatography and liquid scintillation counting. The results were expressed as dpm (mu MPO4)-1 (hr)-1. The IP in MA cells was 44,202 +/- 4,646 and in normal toad cells it was 31,637 +/- 3,613 (P < 0.05). In a separate experiment, cells from 10 paired hemibladders were isolated from normal toads. The cells were treated exactly as above except there were no LiCl in the bath. LiCl was added to all baths after 2 hr and the experimental cells were challenged with IN, PGE2, increases CO2, and aldosterone for 20 min. The IP were quantitated as above. IN treatment stimulated inositol bisphosphate and inositol triphosphate (P < 0.01). PGE2 and increases CO2 also stimulated inositol triphosphate (P < 0.05). Aldosterone did not alter formation of any of the IP fractions. We conclude that MA, IN, PGE2, and increases CO2 stimulate IP formation in cells of toad urinary bladder and inositol triphosphate may be an important second messenger in mediating the response of MA, IN, PGE2, and increases CO2.

Acidosis↗
PubMed1977

Mononuclear cells in Japanese encephalitis virus infection: changes in cells counts and specific fluorescence.

Progressive reduction in blood cell counts was observed in mice inoculated intracerebrally (ic) with Japanese encephalitis (JE) virus. No changes were observed in the blood cell counts of mice inoculated intraperitoneally (ip). Reduction in cell counts after a transient rise was noticed in lymph nodes of mice inoculated by either route but the cell counts returned to normal in lymph nodes of ip inoculated mice by the 8th day post inoculation (p.i.). JE virus antigen was demonstrated by immunofluorescence in mononuclear cells from the blood, spleen and lymph nodes starting from the 3rd and 4th day p.i. in mice inoculated ic and ip, respectively. The number of fluorescent cells increased as the infection progressed. The number of fluorescent spleen cells uas higher in ip than in ic inoculated mice. Live virus could only occasionally be demonstrated in the cells.

Animals↗
PubMed1990

Rapid detection of respiratory syncytial virus and influenza A virus in cell cultures by immunoperoxidase staining with monoclonal antibodies.

Peroxidase-labeled monoclonal antibodies against respiratory syncytial virus (RSV) and influenza A virus were used for immunoperoxidase staining (IPS) of cell cultures inoculated with nasopharyngeal aspirates. Cells were grown in 24-well plates, and specimens were inoculated by low-speed centrifugation. Cultures were incubated for 2 days at 37 degrees C and then fixed, stained, and observed by light microscopy. IPS was compared with standard virus isolation by using cultures of human diploid fibroblasts and Vero, HEp-2, and HeLa cell lines for RSV and Madin-Darby canine kidney cells for influenza A virus; these cultures were inoculated with specimens that were previously stored at -70 degrees C. Of 40 known RSV-positive specimens, 30 were found to be positive on reinoculation by both methods, and an additional 5 specimens were found to be positive by IPS only. Of 190 specimens tested for influenza A virus, 14 were positive by IPS and in tubes, and a further 8 specimens were positive by IPS only. IPS was also compared with direct detection of viral antigens in nasopharyngeal aspirates by a time-resolved fluoroimmunoassay (TR-FIA). Fresh nasopharyngeal aspirates were inoculated into human diploid fibroblasts and Madin-Darby canine kidney cells and tested for RSV and influenza A virus, respectively, by IPS. Of 110 specimens tested for RSV, 37 were positive in total, 32 were positive by IPS, and 33 were positive by TR-FIA. Of 150 specimens tested for influenza A virus, 39 were positive in total, 35 were positive by IPS, and 34 were positive by TR-FIA. IPS of cultures inoculated by centrifugation and incubated for 2 days is a sensitive method for the diagnosis of respiratory virus infections, and 24-well plates allow for the easy processing of a large number of specimens.

Animals↗
PubMed1978

An analysis of conditions allowing Corynebacterium parvum to cause either augmentation or inhibition of natural killer cell activity against tumor cells in mice.

We have analyzed the impact of in vivo administration of Corynebacterium parvum on the mouse immune system against murine tumors, using the natural cytotoxic ability against tumors of normal mouse lymphoid cells as a baseline. A striking difference was found depending on the route of administration. Intravenous inoculation of bacteria would result in a significant decrease or sometimes complete abolition of natural cytotoxicity toward tumor cells of the spleen cells of treated mice. On the other hand, the intraperitoneal route of administration resulted in a dramatic increase in cytolytic ability of the peritoneal exudate cells. Both routes of treatment had the most significant impacts on the local cell population (IV = spleen, IP = peritoneal exudate cells) with only minor effects on other cell populations. Analysis of the spleen cell population from IV-treated mice did also demonstrate a significant reduction in the T lymphocyte function, but in contrast to the natural cytotoxicity this could be corrected for by the removal of suppressor cells of an adherent nature. The lytic cells induced in the peritoneal exudate by the Corynebacterium parvum bacteria were all found to be natural killer, NK, cells with no significant activity found amongst macrophages using short-term cytolytic assays.

Animals↗
PubMed2003

[Compared viability of planctonic bacteria and bacteria in biofilms by flow cytometry].

Study of biofilms adhering to various surfaces shows the presence of several layers of cells. A small percentage can grow immediately. Are the others viable? These cells are in a resting phase and exhibit a metabolic gradient through the depth of the biofilm. In order to assess the health hazard of active recovery of these resting cells, we studied biofilms with two fluorochromes: a fluorescein diacetate derivative, CDF, which detects esterase activity and gives a green fluorescence to cells, and propidium iodide, IP, which enters cells with injured membranes and gives a red fluorescence to nucleic acids. Confocal microscopy can be used to localized red and green cells at various depths in biofilms but flow cytometry is necessary for a semi-quantitative analysis. We focused on parameters required to obtain valid flow cytometry results. After elimination of bacterial and glycocalyx autofluoresce and choosing non-toxic marker concentrations flow cytometry revealed a large proportion of double-marked cells, i.e. cells exhibiting esterase synthesis and membrane injuries. The question is whether these cells are a public health hazard. Can these cells repair their injuries and recover viability when they leave the biofilm? Do they recover metabolic activity, virulence, and sensitivity to antibacterials? Flow cytometry enabled the identification of four levels of viability in oral streptococci biofilms.

Bacteria↗
PubMed1992

Functional heterogeneity and pathogenic significance of interleukin-6 in B-cell lymphomas.

A possible autocrine effect of interleukin-6 (IL-6) on the growth and differentiation of the tumor cells of 55 B-cell lymphomas was examined. Interleukin-6 was detected in a few types of B-cell lymphomas, including polymorphic immunocytoma (PI), small lymphocytic lymphoma (SLL), and immunoblastic lymphoma (IBL) with or without plasmacytoid differentiation. In PI and in IBL with plasmacytoid differentiation (IBL-P), IL-6 was detected only in immunoglobulin-containing plasmacytoid cells, and it was absent from most proliferating (Ki-67/PCNA-positive) lymphoma cells. In SLL, IL-6 was not observed in lymphoplasmacytoid cells; instead, IL-6 was observed in transformed (Ki-67/PCNA-positive) tumor cells in proliferation centers. The lymphoplasmacytoid cells in SLL exhibited a phenotype (IL-6/glutathione-S-transferase-pi [GST-pi]-negative), different from that of normal plasma cells (IL-6-negative/GST-pi-positive) and from the plasmacytoid cells (IL-6/GST-pi-positive) in PI and IBL-P. In IBL without obvious plasmacytoid differentiation, IL-6 was detected in most tumor cells that were highly proliferative (Ki-67/PCNA-positive). In this study, IL-6 was undetectable in most lymphomas related to follicular centers, in lymphoblastic lymphoma, in small noncleaved cell lymphomas of the Burkitt and non-Burkitt types, and in diffuse large cell lymphoma. This finding is compatible with a previous finding that IL-6 mRNA was absent from follicular center cells in reactive lymphoid tissues. The functions of IL-6 in these lymphomas may be quite diverse. It appears that IL-6, as an autocrine factor, is responsible for the plasmacytoid differentiation of lymphoma cells in IP and some IBL (IBL-P). The differentiation of lymphoplasmacytoid lymphoma cells in SLL, however, may not be mediated by an autocrine IL-6 mechanism. Interleukin-6 may provide a growth signal, rather than acting as a differentiation factor, for some IBL cells and for some transformed tumor cells in proliferation centers in SLL.

Cell Differentiation↗
PubMed2005

Effect of glutamine analogue-acivicin on tumor induced angiogenesis in Ehrlich ascites carcinoma.

The inhibition of tumor growth and tumor induced angiogenesis by the glutamine antimetabolite acivicin was evaluated in 6-7 weeks old male Swiss albino mice bearing Ehrlich ascites carcinoma (EAC) transplanted by intraperitoneal (ip) injections of EAC cells. Treatment involving ip injections with two different doses of acivicin (0.05 and 0.41microg/g body weight/day) in saline revealed decrease in tumor volumes and reduced number of blood vessels on peritoneal wall after 10 and 15 days of treatment when compared to control (i.e. injected with saline only). Vascular hyperpermeability was found to be lesser in the treated groups of mice than the control as indicated by the FITC- D and colloidal carbon assay. Serum VEGF level was found to decrease in the drug treated groups both after 10 and 15 days of treatment. The results thus suggest that acivicin may suppress tumoral angiogenesis through regulation of VEGF level.

Angiogenesis Inhibitors↗
PubMed1978

Antibody-dependent lysis of tumor cells in vivo. II. Elimination of chromium-51 as a measurement of cytolysis.

The effect of antibody on tumor cells was studied in vivo by measurement of the rate of elimination of 51Cr in A/J mice inoculated with labeled Ehrlich tumor cells. Mice receiving ip injections of tumor cells and normal serum eliminated 51Cr rapidly during the first 24 hours and at a much slower rate thereafter. This biphasic pattern of elimination was due to the fact that 51Cr predominantly labels small (less than 13,000 mol wt) intracellular molecules, which the mouse rapidly eliminates, whereas larger labeled molecules are eliminated slowly. Antibody to tumor cells significantly accelerated the elimination of 51Cr at concentrations that regularly suppressed tumor growth. Antibody also induced a faster elimination rate in mice treated with cobra venom factor but not in mice treated with silica or inoculated sc with the tumor cells. Unlabeled tumor cells inhibited antibody-induced 51Cr clearance in normal mice but not in proteose peptone-treated mice. These results suggested that peritoneal cells are required in the induction of antibody-dependent cytolysis in vivo. In addition, actively or passively alloimmunized mice exhibited a similar accelerated 51Cr elimination rate when inoculated with the appropriate labeled target cells.

Animals↗
PubMed2000

Female mice heterozygous for IKK gamma/NEMO deficiencies develop a dermatopathy similar to the human X-linked disorder incontinentia pigmenti.

IKK gamma/NEMO is the essential regulatory subunit of the I kappa B kinase (IKK), encoded by an X-linked gene in mice and humans. It is required for NF-kappa B activation and resistance to TNF-induced apoptosis. Female mice heterozygous for Ikk gamma/Nemo deficiency develop a unique dermatopathy characterized by keratinocyte hyperproliferation, skin inflammation, hyperkeratosis, and increased apoptosis. Although Ikk gamma+/- females eventually recover, Ikk gamma- males die in utero. These symptoms and inheritance pattern are very similar to those of incontinentia pigmenti (IP), a human genodermatosis, synthenic with the IKK gamma/NEMO locus. Indeed, biopsies and cells from IP patients exhibit defective IKK gamma/NEMO expression but normal expression of IKK catalytic subunits. This unique self-limiting disease, the first to be genetically linked to the IKK signaling pathway, is dependent on X-chromosome inactivation. We propose that the IKK gamma/NEMO-deficient cells trigger an inflammatory reaction that eventually leads to their death.

Animals↗
PubMed2000

Differential modulation of inositol 1,4,5-trisphosphate receptor type 1 and type 3 by ATP.

Binding of ATP to the inositol 1,4,5-trisphosphate receptor (IP(3)R) results in a more pronounced Ca(2+)release in the presence of inositol 1,4,5-trisphosphate (IP(3)). Two recently published studies demonstrated a different ATP sensitivity of IP(3)-induced Ca(2+)release in cell types expressing different IP(3)R isoforms. Cell types expressing mainly IP(3)R3 were less sensitive to ATP than cell types expressing mainly IP(3)R1 (Missiaen L, Parys JB, Sienaert I et al. Functional properties of the type 3 InsP(3)receptor in 16HBE14o- bronchial mucosal cells. J Biol Chem 1998;273: 8983-8986; Miyakawa T, Maeda A, Yamazawa T et al. Encoding of Ca(2+)signals by differential expression of IP(3)receptor subtypes. EMBO J 1999;18: 1303-1308). In order to investigate the difference in ATP sensitivity between IP(3)R isoforms at the molecular level, microsomes of Sf9 insect cells expressing full-size IP(3)R1 or IP(3)R3 were covalently labeled with ATP by using the photoaffinity label 8-azido[alpha-(32)P]ATP. ATP labeling of the IP(3)R was measured after immunoprecipitation of IP(3)Rs with isoform-specific antibodies, SDS-PAGE and Phosphorimaging. Unlabeled ATP inhibited covalent linking of 8-azido[alpha-(32)P]ATP to the recombinant IP(3)R1 and IP(3)R3 with an IC(50)of 1.6 microM and 177 microM, respectively. MgATP was as effective as ATP in displacing 8-azido[alpha-(32)P]ATP from the ATP-binding sites on IP(3)R1 and IP(3)R3, and in stimulating IP(3)-induced Ca(2+)release from permeabilized A7r5 and 16HBE14o- cells. The interaction of ATP with the ATP-binding sites on IP(3)R1 and IP(3)R3 was different from its interaction with the IP(3)-binding domains, since ATP inhibited IP(3)binding to the N-terminal 581 amino acids of IP(3)R1 and IP(3)R3 with an IC(50)of 353 microM and 4.0 mM, respectively. The ATP-binding sites of IP(3)R1 bound much better ATP than ADP, AMP and particularly GTP, while IP(3)R3 displayed a much broader nucleotide specificity. These results therefore provide molecular evidence for a differential regulation of IP(3)R1 and IP(3)R3 by ATP.

Adenosine Triphosphate↗
PubMed1999

Ischemic preconditioning reduces neutrophil accumulation and myocardial apoptosis.

BACKGROUND: This study tested the hypothesis that ischemic preconditioning (IP) inhibits myocardial apoptosis after a short period of ischemia and reperfusion. METHODS: In 9 anesthetized dogs, the left anterior descending (LAD) coronary artery was occluded for 30 min and reperfused for 3 h (control), while in 9 others, LAD occlusion was preceded by 5 min of occlusion and 5 min of reperfusion (IP). DNA from frozen myocardial tissue samples was extracted, and apoptosis were identified as "ladders" by agarose gel electrophoresis or confirmed histologically using the terminal transferase UTP nick end-labeling (TUNEL) assay. Neutrophil accumulation was detected by measuring cardiac myeloperoxidase activity. RESULTS: Thirty minutes of LAD occlusion caused a significant decrease in blood flow (colored microspheres), which was comparable between groups. In the control group, DNA ladders occurred in the area at risk (AAR) in six out nine experiments. In contrast, DNA laddering in the AAR was not observed in any of the IP group. AAR in the control group showed a greater percentage of apoptotic cells than IP (6.7 +/- 0.9% vs 1.2 +/- 0.2%; p < 0.01). Cardiac myeloperoxidase activity (U/g tissue) was significantly reduced from 0.07 +/- 0.004 in control to 0.04 +/- 0.01 in IP group (p < 0.05). CONCLUSIONS: We conclude that ischemic preconditioning attenuates apoptosis and neutrophil accumulation in the AAR in a model of nonlethal acute ischemia and reperfusion.

Animals↗
PubMed1988

Multiple viral mutations rather than host factors cause defective measles virus gene expression in a subacute sclerosing panencephalitis cell line.

A measles virus (MV) genome originally derived from brain cells of a subacute sclerosing panencephalitis patient expressed in IP-3-Ca cells an unstable MV matrix protein and was unable to produce virus particles. Transfection of this MV genome into other cell lines did not relieve these defects, showing that they are ultimately encoded by viral mutations. However, these defects were partially relieved in a weakly infectious virus which emerged from IP-3-Ca cells and which produced a matrix protein of intermediate stability. The sequences of several cDNAs related to the unstable and intermediately stable matrix proteins showed many differences in comparison with a stable matrix protein sequence and even appreciable heterogeneity among themselves. Nevertheless, partial restoration of matrix protein stability could be ascribed to a single additional amino acid change. From an examination of additional genes, we estimated that, on average, each MV genome in IP-3-Ca cells differs from the others in 30 to 40 of its 16,000 bases. The role of extreme variability of RNA virus genomes in persistent viral infections is discussed in the context of the pathogenesis of subacute sclerosing panencephalitis and of other human diseases of suspected viral etiology.

Animals↗
PubMed1978

Immunization of mice against Fusobacterium necrophorum infection by perenteral or oral administration of vaccine.

Immunization of mice against Fusobacterium necrophorum infection was attempted by using 3 vaccination procedures: (1) intraperitoneal (IP) injection of F necrophorum cells in saline solution, (2) IP injection of cells with added aluminum hydroxide adjuvant, and (3) feeding of a powdered mouse diet containing lyophilized cells. One or 2 weekly IP injections of the bacteria cells (in saline solution) for 3, 6, or 12 weeks resulted in protection of 48.7% to 64.5% of the mice against challenge exposure. Of the 2 control groups (given saline solution only), 100% and 97.4% became infected. Weekly IP injections of bacterial cells in an aluminum hydroxide adjuvant for 3, 6, or 12 weeks resulted in protectivity of 54.1% to 77.5%. Of the control mice (given adjuvant only), 97.5% became infected. Bacterial cells fed to mice at a dose level of 1.5 mg (dry weight)/g of powdered diet for 30 days (4 or 5g of diet each day) resulted in only a delay in the mean time of death as compared with the rapid death of the control mice. The feeding dose of 0.15 mg of cells/g of diet did not delay the mean time of death.

Adjuvants, Immunologic↗
PubMed2001

Robust expression of TNF-alpha, IL-1beta, RANTES, and IP-10 by human microglial cells during nonproductive infection with herpes simplex virus.

Cytokine (TNF-alpha/beta, IL-1beta, IL-6, IL-18, IL-10, and IFN-alpha/beta/gamma) and chemokine (IL-8, IP-10, MCP-1, MIP-1alpha/beta, and RANTES) production during herpes simplex virus (HSV) 1 infection of human brain cells was examined. Primary astrocytes as well as neurons were found to support HSV replication, but neither of these fully permissive cell types produced cytokines or chemokines in response to HSV. In contrast, microglia did not support extensive viral replication; however, ICP4 was detected by immunochemical staining, demonstrating these cells were infected. Late viral protein (nucleocapsid antigen) was detected in <10% of infected microglial cells. Microglia responded to nonpermissive viral infection by producing considerable amounts of TNF-alpha, IL-1beta, IP-10, and RANTES, together with smaller amounts of IL-6, IL-8, and MIP-1alpha as detected by RPA and ELISA. Surprisingly, no interferons (alpha, beta, or gamma) were detected in response to viral infection. Pretreatment of fully permissive astrocytes with TNF-alpha prior to infection with HSV was found to dramatically inhibit replication, resulting in a 14-fold reduction of viral titer. In contrast, pretreatment of astrocytes with IL-1beta had little effect on viral replication. When added to neuronal cultures, exogenous TNF-alpha or IL-1beta did not suppress subsequent HSV replication. Exogenously added IP-10 inhibited HSV replication in neurons (with a 32-fold reduction in viral titer), however, similar IP-10 treatment did not affect viral replication in astrocytes. These results suggest that IP-10 possesses direct antiviral activity in neurons and support a role for microglia in both antiviral defense of the brain as well as amplification of immune responses during neuroinflammation.

Astrocytes↗
PubMed2005

Fertilization and inositol 1,4,5-trisphosphate (IP3)-induced calcium release in type-1 inositol 1,4,5-trisphosphate receptor down-regulated bovine eggs.

It is widely believed that stimulation of the phosphoinositide pathway and production of 1,4,5-inositol trisphosphate (IP(3)) underlies the oscillatory changes in the concentration of intracellular free calcium ions ([Ca(2+)](i)) seen during mammalian fertilization. IP(3) promotes Ca(2+) release in eggs by binding to its receptor, the type-1 IP(3) receptor (IP(3)R-1, also known as ITPR1), a ligand-gated Ca(2+) channel located in the membrane of the endoplasmic reticulum, the main Ca(2+) store of the cell. While IP(3)R-1 has been shown to mediate all Ca(2+) release during mouse fertilization, whether or not it plays such an essential role in fertilization-induced Ca(2+) release in large domestic species such as bovine and porcine is presently not known. Accordingly, we have generated metaphase II bovine eggs with a approximately 70%-80% reduction in the number of intact IP(3)R-1 by inducing receptor down-regulation during oocyte maturation. We did so by injecting the nonhydrolyzable IP(3) analogue, adenophostin A. Functional Ca(2+) release analysis revealed that IP(3)R-1 is the predominant Ca(2+) release channel in bovine eggs, requiring as little as 20% of total intact receptor to mount persistent [Ca(2+)](i) oscillations in response to fertilization, expression of PLCzeta (also known as PLCZ1), and adenophostin A. However, lower concentrations of IP(3) and near-physiological concentrations of porcine sperm extract were unable to trigger [Ca(2+)](i) oscillations in this reduced IP(3)R-1 model. Furthermore, we present evidence that the sensitivity of bovine IP(3)R-1 is impaired at the first embryonic interphase. Together, these results demonstrate the essential role of IP(3)R-1-mediated Ca(2+) release during fertilization in bovine eggs, and identify cell cycle regulatory mechanisms of [Ca(2+)](i) oscillations at the level of IP(3)R-1.

Adenosine↗
PubMed1984

Effect of levamisole on cytotoxic T-cell-mediated immune resistance to L1210 murine leukemia in hyperimmune mice.

The effect of levamisole (LMS) on T-cell-mediated antitumor immunity was examined in adult and aged mice hyperimmune to L1210 leukemia. The immune resistance of aged mice was depressed compared with that of adult mice, which almost completely rejected 5 X 10(7) L1210 cells inoculated IP. A significant level of tumor-specific cytotoxicity was detected in the spleen cells of adult hyperimmune mice by the 51Cr-release assay after in vitro sensitization with mitomycin C-treated L1210 cells. This was mediated by cytotoxic T cells, since in vivo administration of antithymocyte serum or in vitro treatment of the spleen cells with anti-Thy 1.2 antibody and complement abrogated the cytotoxicity completely. In aged mice, however, cytotoxic T-cell activity was lower although the animals were immune to L1210. Administration of LMS (0.38 mg/kg) restored the depressed cytotoxicity of aged mice to the level seen in adult mice. Furthermore, in adult hyperimmune mice LMS augmented T-cell-mediated cytotoxic activity and restored the reduced cytotoxicity caused by in vivo administration of antithymocyte serum. These results indicate that LMS was effective in augmenting T-cell-mediated tumor immunity in immunologically competent or deficient hosts.

Aging↗