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PubMed1996

The mucosa of the middle ear and Eustachian tube in the young rat: number of granulocytes, macrophages, dendritic cells, NK cells and T and B lymphocytes in healthy animals and during otitis media.

To gain a better understanding of immune reactions during otitis media, the middle ear and Eustachian tube mucosa were studied as a unit in young rats with respect to the composition of immunocompetent cells before and after middle ear infection via the tube. Using immunohistology, the distribution of NK cells, important for the defence against viral antigens, and of dendritic cells, known to be most capable of antigen uptake, processing and presentation, was determined. Furthermore, the composition of cells of the unspecific immune system (i.e. granulocytes and macrophages) and the specific immune system (i.e. T and B lymphocytes) was studied. Macrophages and dendritic cells were spread over the whole middle ear mucosa, whereas only few NK cells and T and B lymphocytes and almost no granulocytes were detected. In the Eustachian tube mucosa, immunocompetent cells, with the exception of dendritic cells and macrophages, were only rarely seen. After induction of otitis media by severing the soft palate, immunocompetent cells increased in both the middle ear and Eustachian tube mucosa, but surprisingly they were almost absent from the area of the tubal orifice to the middle ear. The results indicate that immune reactions take place similarly in the Eustachian tube and in the middle ear mucosa.

Animals↗
PubMed1993

Decreased fat content and increased lean in pigs treated with antibodies to adipocyte plasma membranes.

Antibodies were prepared in sheep against purified plasma membranes from pig adipocytes. Western (immuno) blotting revealed reactions of the antisera with a large number of proteins in adipocyte plasma membranes but remarkably few in plasma membranes from muscle, kidney, liver, lung, brain, spleen, and erythrocytes. This illustrated the high degree of specificity the serum had for adipose tissue. When injected into localized subcutaneous sites such antisera were able to cause considerable adipocyte destruction, which resulted in complete loss of adipose tissue from the site for > or = 14 wk. This cell destruction was probably mediated in part by lymphocytic infiltration. Subcutaneous injections were of limited use because of the localized nature of the effects, but, when treatment was administered intraperitoneally, systemic effects were produced that resulted in a 30% reduction in backfat thickness in the region of the last rib and a 25% reduction in fat content of fore- and hind-loin joints that resulted in a significant increase in the percentage of lean tissue. Total feed intake, live weight gain, hot carcass weights, and dressing percentage were unaffected. These results demonstrate the potential for producing long-term reductions in body fat in pigs by an immunization technique that may also provide the unexpected, potential benefit of increased lean deposition. This suggests that fat deposition per se exerts a restrictive influence on lean carcass development.

Adipose Tissue↗
PubMed2006

Preoperative granulocyte/macrophage colony-stimulating factor (GM-CSF) increases hepatic dendritic cell numbers and clustering with lymphocytes in colorectal cancer patients.

Despite surgery with curative intent, approximately 30% of colorectal carcinoma patients will develop liver metastases during follow-up. Synchronous occult micrometastases, tumor cell shedding into the portal circulation and postoperative immune impairment have all been suggested to facilitate outgrowth of liver metastases. In experimental models, increases in both number of resident macrophages of the liver, the so-called Kupffer cells (KC), and tumoricidal capacity of KC were observed after pretreatment with granulocyte/macrophage colony-stimulating factor (GM-CSF), a potent immuno-stimulatory agent. Following perioperative recombinant human GM-CSF (rhGM-CSF), we previously showed activation of the systemic immune response in the postoperative period, which is normally transiently down-modulated after surgery. Therefore, in this pilot study, effects of preoperative rhGM-CSF administration on the composition of human liver immune cell population were evaluated in patients undergoing surgery for colorectal cancer. No difference in KC numbers of rhGM-CSF-treated patients was observed. Importantly, however, a 6-fold increase in dendritic cell (DC) numbers was observed compared to control patients, as quantified by immunohistochemistry of liver biopsies, taken during laparotomy. Furthermore, direct contact between liver CD8+ cells and DC was significantly enhanced in rhGM-CSF-treated patients. Both increases in DC numbers and DC interaction with CD8+ T cells suggest enhanced immunological activation, which may reduce liver metastases formation and ultimately improve survival after initial colorectal surgery.

Cell Adhesion↗
PubMed2004

Factors affecting engraftment of allogeneic hematopoietic stem cells after reduced-intensity conditioning.

Several factors influence the engraftment of allogeneic hematopoietic stem cells (HSC). Recently, there has been increased utilization of transplant-conditioning regimens that use reduced doses of chemotherapy and radiation that are considered to be non-myeloablative. These non-myeloablative (or reduced-intensity) allogeneic HSC transplants (RIST) decrease early post-transplant complications, but they are associated with higher incidences of mixed chimerism and graft rejection compared with transplantation after myeloablative condition-ing. RIST provides a unique opportunity to study allogeneic HSC engraftment. In particular, host immune status and stem cell graft composition have emerged as important factors affecting engraftment after RIST Based on these observations, it has been hypothesized that conditioning regimens and allograft composition can be tailored to an individual patients immune and disease status prior to transplant.

Animals↗
PubMed1999

Distribution of immune cells in the epididymis of the aging Brown Norway rat is segment-specific and related to the luminal content.

Remarkable changes occur during aging in the testis and epididymis of the Brown Norway rat. A dramatic increase in the number of halo cells, which are present in the epididymal epithelium and originate from the immune system, is found in animals of increasing age. Halo cells have been postulated to be either lymphocytes or monocytes. We hypothesized that halo cells are a mixture of different immune cells and that their relative composition changes with age. To verify this hypothesis, markers for helper T lymphocytes, cytotoxic T lymphocytes, B lymphocytes, and monocytes-macrophages were used to identify the major categories of immune cells in the epididymides of Brown Norway rats ranging in age from 3 to 24 mo. The numbers of immunocompetent cells in the epididymis were determined in relation to age, epididymal segment, and luminal content. We found that monocytes, helper T lymphocytes, and cytotoxic T lymphocytes belong to the population of halo cells. In addition, a segment-specific increase with age in the number of these immune cells was noted. Finally, we report a segment-specific recruitment of cytotoxic T lymphocytes and monocytes-macrophages in the epididymal epithelium of aged rats whose epididymal lumen contained few spermatozoa. We postulate that accumulation of damaged epithelial cells and antigens of germ cell origin, leaking through a dysfunctional blood-epididymis barrier, may contribute to the active recruitment of immune cells with age.

Aging↗
PubMed1999

Dose-dependent effects of dietary gamma-linolenic acid on rat spleen lymphocyte functions.

Feeding rodents a diet rich in evening primrose oil (EPO), which contains 5-10 g gamma-linolenic acid (GLA)/100 g total fatty acids, has been shown to decrease lymphocyte proliferation and natural killer cell activity. However, EPO contains a very high level of linoleic acid which itself can affect lymphocyte functions and it is not clear to what extent the effects of EPO can be attributed to GLA. The current study investigated the effect of two levels of GLA in the rat diet upon immune cell functions; the level of linoleic acid was maintained below 30 g/100 g total fatty acids. Weanling rats were fed on high fat (178 g/kg) diets which contained 4.4 g or 10 g GLA/100 g total fatty acids in place of a proportion of linoleic acid. The total polyunsaturated fatty acid content and the n-6 to n-3 polyunsaturated fatty acid ratio of the diet were maintained at 35 g/100 g total fatty acids and 7, respectively. The fatty acid compositions of the serum and of spleen leukocytes were markedly influenced by that of the diet, with an increase in the proportions of GLA and dihomo-gamma-linolenic acid when the diets containing GLA were fed; these diets also increased the proportion of arachidonic acid in spleen leukocytes. Spleen lymphocyte proliferation in response to concanavalin A was significantly reduced (by 60%) by feeding the diet containing the higher level of GLA, but not by the diet containing the lower level of GLA. Spleen natural killer cell activity and prostaglandin E (PGE) production by spleen leukocytes were not significantly affected by inclusion of GLA in the diet, although there was a tendency towards decreased natural killer cell activity by cells from rats fed the high GLA diet. Thus, this study shows that dietary GLA is capable of altering the fatty acid composition of cells of the immune system and of exerting some immunomodulatory effects, but that the level of GLA in the diet must exceed 4.4 g/100 g total fatty acids for these effects to become apparent.

Animals↗
PubMed2002

HEPC-based liposomes trigger cytokine release from peripheral blood cells: effects of liposomal size, dose and lipid composition.

The immune response caused by liposome stimulation was studied by assessing the level of several cytokines released from human peripheral blood cells. Liposome stimulation resulted in the release of IL-6, IL-10, IL-1beta, TNF-alpha and IFN-gamma. The size of the liposomes affected the degree of the cytokine releases with larger sized liposomes causing higher levels of cytokine induction. In addition, it appears that the lipid composition of liposomes had no effect on the degree of cytokine release. The release of cytokines occurred even in the absence of serum, suggesting that serum proteins did not contribute to liposome stimulation in peripheral blood cells. The release of cytokines induced by liposome stimulation was inhibited by the presence of either protein kinase-C (PKC) or protein tyrosine kinase (PTK) inhibitor, but not by the presence of an endocytosis inhibitor. This indicates that signal transduction via PKC or PTK is necessary, in order for human peripheral blood cells to release cytokines (IL-6, IL-10, IL-1beta, TNF-alpha and IFN-gamma) as the result of liposome stimulation. These quantitative data on the release of cytokines by liposomal stimulation provide useful information for the development of rational drug delivery systems and the safety of cytokine induction via the use of liposomes.

Cytokines↗
PubMed1981

Three polyethylene glycol dependent methods for the detection or circulating immune complexes in pathological sera: comparison with the Raji cell method.

A composite method using polyethylene glycol (PEG) and different markers for detecting circulating immune complexes (CIC) is described. The markers used are bovine conglutinin (RK-BA), C1q (C1q-BA) and IgG, IgM quantitation of PEG precipitate (RID-Ig). A composite scoring system is used in interpreting results from individual assays. The sensitivity of multiple PEG methods (MPM) was determined in 418 serum samples and compared with Raji cell assay in 204. Correlations between individual assays, viz., RK-BA-C1q-BA, RID-Ig and Raji cell test in several disease conditions including rheumatoid arthritis, glomerulonephritis, post-renal transplantation, maintenance haemodialysis, multiple sclerosis and normal pregnancies were computed. The relative discriminatory ability of a single PEG technique to differentiate normal from pathological sera in these disease states was observed in comparison with the composite PEG index. This index gives an improved assessment of abnormal sera, is simple and sensitive and has some advantages over biological techniques such as the Raji cell assay.U

Antigen-Antibody Complex↗
PubMed2005

Composite islet-endothelial cell grafts: a novel approach to counteract innate immunity in islet transplantation.

An instant blood-mediated inflammatory reaction (IBMIR) is elicited when islets come in contact with blood after intraportal transplantation. In contrast, endothelial cells (EC) readily tolerate contact with blood. A conceivable strategy to overcome IBMIR would be to create composite islet-EC grafts. Human islets were co-cultured with primary human aortic endothelial cells (HAEC) for 2-7 days to obtain 50-90% coverage. HAEC-coated islets were exposed to ABO-identical blood and analyzed with regard to clotting time, signs of inflammation and cell infiltration. Composite islet-HAEC graft survival was assessed after transplantation to athymic (nu/nu) nude mice. Exposed to blood, HAEC-coated islets induced less activation of coagulation and complement compared to control islets. Also, platelet and leukocyte consumption in blood was decreased. Clots with entrapped HAEC-coated islets showed less infiltration of CD11b+ cells. The extent of protection correlated to the level of HAEC coverage. Transplanted composite grafts stained positive for insulin and PECAM-1 demonstrating presence of both islets and HAEC within the islet graft 7 weeks after transplantation. Composite islet-HAEC grafts reduce all components of IBMIR. Refinement of the technique will allow introduction of composite islet-EC grafts in clinical islet transplantation, using autologous EC expanded in vitro and kept frozen until allogeneic islets become available for that specific recipient.

Animals↗
PubMed1987

Changes in pulmonary surfactant composition following MACC chemotherapy for lung carcinoma.

Many antineoplastic drugs can derange lung structures, cause necrosis of type I pneumocytes, abnormal proliferation of type II alveolar epithelial cells, and, occasionally, accumulation of inflammatory and immune effector cells. Since type II cells secrete lung surfactant, treatment may alter surfactant composition. In 8 patients with nonresectable lung cancer, we performed bronchoalveolar lavage before and after MACC polychemotherapy (methotrexate, doxorubicin HCl, cyclophosphamide and lomustine). Before treatment, cellular composition and the phospholipid and fatty acid constituents of lavage surfactant were similar to those found in control subjects. After MACC polychemotherapy there was, in all patients, a mild decrease in the number of immune effector cells, without changes in the relative proportion of cell types. In addition, MACC therapy resulted in a significant decrease of phosphatidylcholine levels, and increased levels of phosphatidylglycerol, whereas the levels of palmitic lavage surfactant were decreased. These MACC treatment abnormalities of the phospholipid and fatty acid composition of lung surfactant may reflect preclinical pulmonary toxicity. The decrease in the numbers of bronchoalveolar cells suggests that the changes in surfactant composition may be chemically induced rather than immune mediated.

Adult↗
PubMedDate not supplied

Inhalatory anesthetic (halothane) associated changes in the immune response in mice.

The extent of surgery, the patient's age, health status and other factors may contribute to alteration of the immune system during anesthesia and surgery. In addition, inhalatory anesthetics may cause acute and chronic toxicity because of the production of intermediate and end metabolic compounds. The present work was undertaken to evaluate, both in vivo and in vitro, if repeated doses of halothane were able to affect the immune response in a murine model developed at our laboratory. Weekly doses of halothane were administered to mice subjected to no surgery and three days after the last anesthetic-exposure, several immunologic parameters were assessed. Results on the in vivo response to sheep red blood cells showed that halothane treatment increased the amount of specific antibody secreting B-cells, without affecting the delayed type hypersensitivity reaction to the same antigen. In vitro studies on spleen cell composition showed that halothane re-exposure diminished the number of CD4+, CD8+ and B-cells. Such changes were not translated into alterations on the mitogen-driven lymphoproliferation, as well as macrophage phagocytic and lytic functions. Our results indicate that halothane re-exposure is able to modulate the immune response affecting both the number of antibody secreting cells involved in a specific in vivo response, and the splenic lymphoid cell composition. Since such halothane-induced immune alterations might bias the results of a wide range of physiological research, even those involving other systems, a careful selection of the anesthetic agent and methods by which the compound is administered is advisable.

Anesthetics, Inhalation↗
PubMed1983

IgE on rat pleural and peritoneal mast cells; relation to serum IgE.

Brown Norway rats were immunized with trinitrophenylated ovalbumin (TNP-OVA). TNP-specific and total IgE in serum and in acid eluates of pleural and peritoneal mast cells were determined by radioimmunoassay. The IgE load of peritoneal mast cells was significantly higher than the IgE load of pleural mast cells. 8-9 days after immunization, the ratio specific/total IgE for cell-bound IgE was smaller than this ratio for free circulating IgE. The composition of IgE on mast cells that were isolated 8-9 days after immunization was better reflected by the composition of serum IgE on the day before isolation than by the composition of serum IgE at the time of isolation of the mast cells. Therefore, we conclude that (1) IgE on mast cells is not in rapid equilibrium with free circulating IgE, and (2) the composition of IgE on mast cells lags at least 1 day behind that of serum IgE.

Animals↗
PubMed1971

The action of cortisone acetate on cell-mediated immunity to infection. Suppression of host cell proliferation and alteration of cellular composition of infective foci.

Pulse labeling with tritiated thymidine shows that the response in the mouse to infection with L. monocytogenes includes a large increase in the division of lymphoid cells in the spleen, an increase in the division of macrophages in the liver, and an accumulation of monocyte-derived macrophages at infective foci in the tissues. A single 2.5 mg dose of cortisone acetate given at the beginning of infection greatly delays and suppresses these three components of the host response. The unrestricted bacterial multiplication which follows cortisone treatment is ultimately because of a failure of monocyte-derived macrophages to accumulate at infective foci where they normally express immunity. The accumulation of polymorphs at these sites, in contrast, is enhanced. It is argued that cortisone acetate prevents the accumulation of monocytes at infective foci indirectly by suppressing the production in the spleen of immunologically-committed lymphocytes which are needed to mediate the cellular events at infective foci.

Animals↗
PubMedDate not supplied

[New immunology--immunology of pattern recognition receptors].

Pattern recognition receptors (PRRs) have been found on all cells of the body--cells of the innate and adaptive immune systems, epithelial and endothelial cells, keratinocytes, etc. PRRs can recognize specific molecular structures of microorganisms as well as allergens and other substances. The interaction with ligands of foreign microorganisms activates PRRs, after which host cells start to produce cytokines to both specifically activate innate immunity and to control adaptive immune reactions. On the other hand, no immune response develops against microorganisms of the normal microflora. Practically, the development of all immune responses is controlled by PRRs. These responses start in epithelial cells, skin cells, and vascular epithelial cells, which meet alien first. The immune system uses these cells to control the composition of normal microflora. Accordingly, the definition of immune system functions should be complemented by the regulation of body's microflora in addition to the protection from alien and altered self.

Allergy and Immunology↗
PubMed2002

Optimizing engraftment--source and dose of stem cells.

In recent years, the use of antibodies to measure CD34(+) cells and the availability of peripheral blood (PB) and umbilical cord blood (CB) as additional stem cell sources other than bone marrow (BM) has increased interest in determining the impact of stem cell source and dose on the outcome of allogeneic stem cell transplantation. In addition to differences in their stem cell content, transplants from the three sources differ in the composition and state of activation of immune cells. As a consequence, BM, CB, and PB transplants have different kinetics of hematological recovery, the most rapid engraftment being observed with PB and the slowest with CB. Stem cell source also incurs different risks for developing graft-versus-host disease (GVHD): PB transplants show a possible increase in acute and a definite increase in chronic GVHD compared with BM. CB transplants have a favorably low risk of GVHD even in mismatched transplants. Stem cell dose in an independent factor in transplants from any source, determining engraftment, transplant-related mortality and risk of leukemic relapse. These findings are of clinical importance-an understanding of the impact of stem cell source and dose is essential to obtain optimum conditions for a successful outcome after transplant.

Blood Cells↗
PubMed2026

Plasma lipid species, immune cell traits, and gastric cancer risk: A Mendelian randomization study.

Plasma lipid composition has been linked to multiple cancers, yet its causal contribution to gastric cancer and the potential intermediary role of immune cells remain unclear. We aimed to clarify these relationships and identify specific lipid and immune cell traits that either protect against or promote gastric cancer. We performed a 2-sample, 2-step Mendelian randomization analysis using summary statistics from large genome-wide association studies of gastric cancer (1423 cases, 3,14,193 controls), plasma lipidomics (179 molecular species), and 731 immune cell phenotypes. Independent, genome-wide significant single-nucleotide variants served as instrumental variables. First, we estimated the causal effects of each plasma lipid on gastric cancer. Then, we explored the potential intermediary role of lipid-associated immune cell traits using a 2-step Mendelian randomization framework. Two lipids - phosphatidylethanolamine (18:0 0:0) and phosphatidylcholine (O-18:0 16:1) - were causally associated with a lower risk of gastric cancer. Three immune cell traits (CD8br and CD8dim %leukocyte, IgD on IgD+ CD38- and CD3 on CD28- CD8br) similarly showed protective effects. In contrast, phosphatidylcholine (O-16:1 18:2), triacylglycerol (49:1), triacylglycerol (56:3), and triacylglycerol (56:4) increased gastric cancer risk, as did immune traits such as TD DN (CD4-CD8-)AC, CD19 on memory B cell, CD28 on CD39+ activated Treg, CD45 on CD4+, CD127 on CD28+DN(CD4-CD8-) and CCR2 on CD14+CD16+ monocyte. Exploratory mediation analyses found no statistically significant evidence that immune cell traits mediated the effects of plasma lipids on gastric cancer risk. Specific phosphatidylethanolamines and phosphatidylcholines confer protection against gastric cancer, whereas several triacylglycerols increase risk. However, exploratory mediation analyses provided no statistically significant evidence that immune cell traits mediated these associations.

Humans↗
PubMed1992

Dietary n-3 fatty acids reduce antibody-dependent cell cytotoxicity and alter eicosanoid release by chicken immune cells.

The overall goal of the present study was to determine whether the incorporation of n-3 fatty acids into poultry rations would alter the immune response of broiler chickens. Female broiler chicks were fed a corn and soybean meal-based diet to which one of four dietary fats were added: lard (LA), corn oil (CO), flaxseed oil (SO), or menhaden fish oil (FO). The latter two fat sources are rich in n-3 polyunsaturated fatty acids (PUFA). Enriching the diet with n-3 PUFA did not alter the primary or secondary antibody response of broiler chickens to sheep red blood cells. Dietary fat source had no effect on antibody-dependent cell cytotoxicity (ADCC) by peripheral blood leukocytes, but ADCC by splenocytes was 50% lower in chickens fed SO and FO compared with LA and CO (P less than .005). As expected, the fatty acid profile of the isolated immune cells reflected the fatty acid composition of the dietary fats fed. Basal release and calcium ionophore (A23187)-stimulated (10 microM) release of thromboxane B were significantly lower (P less than .05) in the SO and FO groups compared with the LA and CO groups. Total leukotriene B release was not significantly altered by dietary fat source. In conclusion, feeding broiler chickens diets rich in n-3 PUFA reduced ADCC of splenocytes and altered eicosanoid production by isolated immune cells.

Animals↗
PubMed1998

Eicosapentaenoic and docosahexaenoic acids alter rat spleen leukocyte fatty acid composition and prostaglandin E2 production but have different effects on lymphocyte functions and cell-mediated immunity.

Weanling rats were fed on high-fat (178 g/kg) diets which contained 4.4 g alpha-linolenic (ALA), gamma-linolenic, arachidonic (ARA), eicosapentaenoic (EPA), or docosahexaenoic acid (DHA)/100 g total fatty acids. The proportions of all other fatty acids, apart from linoleic acid, and the proportion of total polyunsaturated fatty acids (PUFA) (approximately 35 g/100 g total fatty acids) were constant, and the n-6 to n-3 PUFA ratio was maintained as close to 7 as possible. The fatty acid compositions of the serum and of spleen leukocytes were markedly influenced by that of the diet. Prostaglandin E2 production was enhanced from leukocytes from rats fed the ARA-rich diet and was decreased from leukocytes from the EPA- or DHA-fed rats. Replacing dietary ALA with EPA resulted in diminished ex vivo lymphocyte proliferation and natural killer (NK) cell activity and a reduced cell-mediated immune response in vivo. In contrast, replacing ALA with DHA reduced ex vivo lymphocyte proliferation but did not affect ex vivo NK cell activity or the cell-mediated immune response in vivo. Replacement of a proportion of linoleic acid with either gamma-linolenic acid or ARA did not affect lymphocyte proliferation, NK cell activity, or the cell-mediated immune response. Thus, this study shows that different n-3 PUFA exert different immunomodulatory actions, that EPA exerts more widespread and/or stronger immunomodulatory effects than DHA, that a low level of EPA is sufficient to influence the immune response, and that the immunomodulatory effects of fish oil may be mainly due to EPA.

Animals↗