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Relation between the fatty acid composition of peripheral blood mononuclear cells and measures of immune cell function in healthy, free-living subjects aged 25-72 y.

BACKGROUND: There is little information about the relation between the fatty acid composition of human immune cells and the function of those cells over the habitual range of fatty acid intakes. OBJECTIVE: The objective of the study was to determine the relation between the fatty acid composition of human peripheral blood mononuclear cell (PBMC) phospholipids and the functions of human immune cells. DESIGN: One hundred fifty healthy adult subjects provided a fasting blood sample. The phagocytic and oxidative burst activities of monocytes and neutrophils were measured in whole blood. PBMCs were isolated and used to measure lymphocyte proliferation in response to the T cell mitogen concanavalin A and the production of cytokines in response to concanavalin A or bacterial lipopolysaccharide. The fatty acid composition of plasma and PBMC phospholipids was determined. RESULTS: Wide variations in fatty acid composition of PBMC phospholipids and immune cell functions were identified among the subjects. The proportions of total polyunsaturated fatty acids (PUFAs), of total n-6 and n-3 PUFAs, and of several individual PUFAs in PBMC phospholipids were positively correlated with phagocytosis by neutrophils and monocytes, neutrophil oxidative burst, lymphocyte proliferation, and interferon gamma production. The ratios of saturated fatty acids to PUFAs and of n-6 to n-3 PUFAs were negatively correlated with these same immune functions. The relation of PBMC fatty acid composition to monocyte oxidative burst was the reverse of its relation to monocyte phagocytosis and neutrophil oxidative burst. CONCLUSION: Variations in the fatty acid composition of PBMC phospholipids account for some of the variability in immune cell functions among healthy adults.

Adult↗

Maternal dietary n-3 fatty acids alter immune cell fatty acid composition and leukotriene production in growing chicks.

The effect of feeding different amounts of n-6 and n-3 fatty acids (FA) to hens on immune tissue FA composition and leukotriene production of hatched chicks was investigated. Hens were fed diets supplemented with either 3.0% sunflower oil (Diet I), 1.5% sunflower+1.5% fish oil (Diet II), or 3.0% fish oil (Diet III) for 46 days. The hatched chicks were fed a diet containing C18:3n-3, but devoid of longer chain n-6 and n-3 FA, for 21 days. Spleen docosahexaenoic acid (DHA) content was higher in chicks from hens fed Diet III (P<0.05). The bursa content of arachidonic acid was lower in chicks hatched from hens fed Diet III (P<0.05), and the ratio of n-6 to n-3 FA was significantly higher in bursa of chicks hatched to hens fed Diet I (P<0.05). Eicosapentaenoic acid (EPA) and DHA contents were higher in bursa of chicks hatched from hens fed Diet III (P<0.05). Thrombocytes from chicks hatched to hens fed Diet III produced the most leukotriene B(5) (LTB(5)). The ratio of LTB(5) to LTB(4) concentrations was also highest (P<0.05) in chicks hatched to hens fed Diet III. These results indicate that modulating maternal dietary n-6 and n-3 FA may alter leukotriene production in chicks, which could lead to less inflammatory-related disorders in poultry.

Animals↗

The effect of increasing levels of dietary fish oil rich in eicosapentaenoic and docosahexaenoic acids on lymphocyte phospholipid fatty acid composition and cell-mediated immunity in the mouse.

The influence of increasing intakes of fish oil on spleen leucocyte phospholipid fatty acid composition and cell-mediated immunity was studied in the mouse using a popliteal lymph node assay technique. The immune response was suppressed by 160 g fish oil/kg diet, but not by lower doses. The proportion of 20:5n-3 in spleen leucocyte phospholipid increased from 0.14 in the controls to 3.8, 7.2, 8.5 and 9.4% in the animals fed on 25, 50, 100 and 160 g fish oil/kg diet; the proportion of 22:6n-3 increased from 5.1 in the controls to 12.1, 12.2, 12.8 and 12.9% respectively. It is concluded that moderate intakes of fish oil are not immunosuppressive.

Animals↗

Chronic feline leukemia virus infection alters arachidonic acid proportions in vivo and in vitro.

The polyunsaturated omega-6 fatty acid, arachidonic acid ([AA] 20:4n-6), is both the key of the immunoregulatory substances, prostaglandins, and leukotrienes, and an essential component of immune cell membrane phospholipids, providing stability and flexibility to ensure cellular function. To explore possible effects of the physiological burden of viral replication in chronic viral infections on AA availability, plasma total esterified fatty acid (FA) proportions were measured in the feline leukemia (FeLV) model. Plasma FA profiles of 12 specific-pathogen-free cats with chronic infections with Rickard strain feline leukemia virus (FeLV-R) were compared with 12 age- and sex-matched uninfected specific-pathogen-free cats at 4 months after infection. A significant decrease from normal of average AA proportion was found in FeLV-R-infected cat plasma, while other major FA (palmitic, stearic, and oleic and omega-3 FA normally remained present until near death. Since plasma FA content rapidly affects circulating immune cell membrane composition and since FeLV infection also targets immune cells, we compared FA profiles of feline T4-thymic lymphoma 3201 cell membranes that were infected with virulent FeLV-R or less virulent FeLV-A, at 20 days after viral inoculation with sham-inoculated uninfected 3201 cells. Significantly altered FA proportions and ratios of saturated to unsaturated FA found in infected cell membranes were similar to plasma FA changes and paralleled the virulence of the FeLV inoculum. Altered postinfection FA proportions may impart serious functional defects to the immune cells of chronic FeLV-infected cats, contributing to the inability of their immune systems to eliminate FeLV by depleted plasma AA stores and modified cell membrane composition. Decreased AA availability may be an important factor in the cachexia and fatal outcome of FeLV infection.

Animals↗

Admission whole-blood transcriptomic characterization of a neutrophil-predominant systemic immune response in patients with acute traumatic brain injury.

BACKGROUND: Acute traumatic brain injury (TBI) is accompanied by systemic immune responses, but their whole-blood transcriptomic features at hospital arrival remain incompletely characterized. We aimed to characterize these features in patients with acute TBI compared with healthy controls. METHODS: In this single-center prospective observational study, we performed whole-blood RNA sequencing on hospital-arrival samples from 42 patients with acute TBI and 21 healthy controls. Analyses included differential expression (limma-voom; FDR < 0.05, |log2FC| > 0.7), functional enrichment, Ingenuity Pathway Analysis, CIBERSORTx LM22 deconvolution, and per-sample neutrophil degranulation signature scoring. RESULTS: Differential expression analysis identified 996 upregulated and 863 downregulated genes, with marked upregulation of inflammation-, innate immunity-, and neutrophil-related genes including DUSP1, HMGB2, MMP9, and S100A8. Canonical pathways with positive IPA z-scores included Neutrophil degranulation, Neutrophil Extracellular Trap Signaling Pathway, and Toll-like Receptor Signaling; upstream regulators included TNF, IL1B, IFNG, and STAT3. Deconvolution identified 7 of 22 differing subsets (q < 0.05), with relatively higher myeloid and lower lymphoid fractions in TBI. The Neutrophil degranulation signature score correlated with Injury Severity Score within TBI (Spearman &#x3c1; = +0.55; q < 0.001). CONCLUSIONS: Admission whole-blood transcriptomics characterized a neutrophil-predominant systemic transcriptional response in patients with acute TBI. This response was also evident among patients without major extracranial injury and was associated with total ISS. However, because the study lacked an appropriately matched non-TBI trauma comparator, the findings should be interpreted as a descriptive characterization of a systemic injury response accompanying TBI and do not establish a TBI-specific molecular signature or mechanism.

gene expression↗

[Tumor-induced immunosuppression].

Tumor immunology is based on two essential concepts: immune surveillance, which implicate the host immune reactions against tumor cells, and tumor immune escape, which refers to the tumor-cell evasion process against the host immune system. The notion that a deficit in immune cell functions permits tumor growth has received experimental support with the discovery of several different biochemical defects in T lymphocytes that infiltrate cancers. Furthermore, expression of self-antigens on the tumor surface impose potential barriers to the development of effective immune response. Tumors are able to overcome immune surveillance by changing the polarity of effectors cells, thus down-regulating the proliferation of tumor-specific cytotoxic T cells, or altering the effector compositions of immune cells within the tumor milieu, or both. Understanding the interaction between cancer cells and host immune cells is of importance for clinical applications or immunotherapy in cancer treatment.

Animals↗

Tumor immunology--when a cancer cell meets the immune cells.

Tumor immunology consists of two essential concepts: immune surveillance, which specifies the host immune reactions against tumor cells, and tumor immune escape, which refers to the tumor-cell evasion process against the host immune system. Effective antitumor immunity by the host immune surveillance is supposed to be dependent on the identification of tumor antigens. In the process of malignant transformation, genetic mutations with aberrant expression of cancer-related genes and protein products are potentially immunogenic, which may serve as rejection antigens. Several scenarios are proposed to be responsible for tumor immune-escape mechanisms. The elucidation of the immune deficit against cancer progression has been a difficult task and no solitary mechanism explains the complicated cancer-host immune interactions. Cancer cells may overcome immune surveillance through a common but effective pathway, either by changing the polarity of effector cells, thus down-regulating the proliferation of tumor-specific cytotoxic T cells, or altering the effector compositions of immune cells within the tumor milieu, or both. Understanding the interaction between cancer cells and host immune cells within the tumor milieu is of importance for further clinical applications of immunotherapy in cancer treatment.

Antigens, Neoplasm↗

Structure of IL-13 receptor: analysis of subunit composition in cancer and immune cells.

The structure of IL-13 receptor (IL-13R) is currently under investigation. Recently, two different human IL-13R chains, termed here IL-13R alpha and -alpha' have been cloned. We have examined various cancer and normal cell lines for the presence of mRNA for IL-13R alpha and alpha, as well as IL-4R p140 (termed beta chain) and IL-2R gamma c chains. In renal cell carcinoma, glioblastoma and ovarian carcinoma (IGROV-1) cell lines, both IL-13R alpha and alpha chains were expressed (type I IL-13R). In epidermoid, colon, ovarian adenocarcinoma (PA-1) and normal mouse fibroblast (COS7) cell lines, only IL-13R alpha' was expressed (type II IL-13R). In hematopoietic TF-1 and EBV-immortalized normal B cell lines only IL-13R alpha' but not alpha chain was expressed along with gamma c (type III or type IV IL-13R). IL-13R alpha' chain was faintly detected in human T cells. All cells expressed the IL-4Rp140 beta chain. These data provide a direct support for our model of IL-13R which consists of three different forms composed of different subunits.

Animals↗

The lamina adventitia is the major site of immune cell accumulation in standard chow-fed apolipoprotein E-deficient mice.

OBJECTIVE: Cells of adaptive immunity have been implicated in atherogenesis. Though substantial information is available on immune cells in atherosclerotic lesions of the lamina intima, cells in the lamina adventitia have received less attention. METHODS AND RESULTS: The composition of immune cells in the innominate artery and abdominal aorta was examined in young, adult, and old apolipoprotein (apo) E(-/-) and wild-type mice on standard mouse chow. In the innominate artery of apoE(-/-) mice, adventitial T cells increased at 32, 52, and 78 weeks exceeding those of the intima by 6-, 24-, and 85-fold. Single T cells dominated in young mice, later T/B cell clusters emerged, and lymphoid-like structures reminiscent of inflammatory follicles formed preferentially in the abdominal aorta of old mice. Follicles contained organized sets of immune response-regulating cells: Interdigitating dendritic cells, T cell effectors, proliferating B cells, and plasma cells. Adventitial T cell inflammation was associated with a marked increase in transcripts of the chemokine MIP-1alpha in the aorta but not in spleen or liver. CONCLUSIONS: Adventitial lymphocyte infiltration and formation of inflammatory follicle-like structures in the abdominal aorta of old apoE(-/-) mice point to the adventitia as a site of local adaptive immune reactions during atherogenesis in hyperlipidemic mice.

Age Factors↗

Upregulation of cathepsin W-expressing T cells is specific for autoimmune atrophic gastritis compared to other types of chronic gastritis.

AIM: To investigate a pathophysiological role of cathepsin W (CatW), a putative thiol-dependent cysteine protease, which is specifically expressed in cytotoxic lymphocytes, in different types of chronic inflammation of the gastric mucosa. METHODS: Gastric and duodenal biopsies of patients with Helicobacter pylori (H pylori)-associated active gastritis (Hp, n = 19), chemically induced reactive gastritis (CG, n = 17), autoimmune atrophic gastritis (AIG, n = 20), lymphocytic corpus gastritis (LG, n = 29), celiac disease (CD, n = 10), and corresponding controls (n = 24) were analyzed by immunohistochemistry for the expression of CatW and CD45. Furthermore, immunohistochemical double staining with anti-CD3 and anti-cathepsin was performed for the samples of AIG. RESULTS: Median values of CatW-expressing cells among CD45-positive immune cells were between 2% and 6% for normal gastric mucosa, CG, and LG, whereas the corresponding value was significantly increased for AIG (24.7%, P<0.001) and significantly decreased for HP (0.7%, P<0.05). Double staining with anti-CD3 and anti-CatW antibodies revealed that >90% of CatW-expressing cells in gastric mucosa of AIG were T cells. Duodenal mucosa had significantly more CatW/CD45-positive cells than normal gastric mucosa (median: 17.8% vs 2%, P<0.01). The corresponding proportion of CatW/CD45-postive cells was decreased in CD compared to duodenal mucosa (median: 2.1% vs 17.8%, P<0.05). CONCLUSION: The opposite findings regarding the presence of CatW-positive cells in AIG (increase) and CD (decrease) reflects the different cellular composition of immune cells involved in the pathogenesis of these diseases.

Autoimmune Diseases↗

Composition of the lymphoid cell populations from omental milky spots during the immune response in C57BL/Ka mice.

The lymphoid cell composition of milky spots was analyzed in unprimed mice before and after i.p. immunization with sheep red blood cells. Milky spots contained surface immunoglobulin-positive B lymphocytes, and T cells of the helper and cytotoxic phenotype. After secondary antigen challenge the number of lymphocytes increased up to 40-fold, B and T cells were found to segregate into distinct areas in situ, and lymphocytes were found to associate with I-A-negative stromal cells in vivo. These findings qualify milky spots as a peripheral lymphoid organ exhibiting a remarkable change in number and composition of lymphocytes in response to a local antigen stimulus.

Animals↗

Upregulation of tumor necrosis factor-alpha by stress and substance p in a murine model of allergic airway inflammation.

OBJECTIVE: Clinical observation has suggested that stress and asthma morbidity are associated, though underlying mechanisms are not clearly understood. After having established a mouse model of stress-exacerbated allergic airway inflammation, we demonstrated a stress-mediating role for neurokinin-1 receptor, the main substance P (SP) receptor. Here, our aim was to investigate the influence of stress or exogenously applied SP on airway inflammation and on the local cytokine production of immune cells. METHODS: BALB/c mice were systemically sensitized to ovalbumin (OVA) and repeatedly challenged with OVA aerosol. Sound stress was applied to the animals for 24 h, starting with the first airway challenge. Alternatively, one group of non-stressed mice received intranasal SP before airway challenges. Cell numbers were determined in bronchoalveolar lavage (BAL) fluid. Leukocytes from mediastinal lymph nodes were analyzed by flow cytometry to determine the percentages of T cells producing interleukin-4, interferon-gamma and tumor necrosis factor-alpha. RESULTS: In BAL fluids of stressed or SP-treated animals, significantly higher total cell counts were found compared to non-stressed mice. In lymph nodes, the percentage of TNF-alpha-positive T cells was higher in stressed mice and mice after application of SP. In contrast, the influence of stress did not increase the percentages of interferon-gamma-positive CD3+ cells, meanwhile the application of SP increased the percentages of T cells positive for this cytokine. CONCLUSION: Our data provide further evidence for a stress-mediating neuroimmunological pathway that, putatively via SP, is able to influence the composition of immune cells in different compartments of allergic airway inflammation.

Acoustic Stimulation↗

[Study on regulatory effect of composite taixian tablet on immune function of red blood cell in patients with oral lichen planus].

OBJECTIVE: To explore the regulatory effect of Composite Taixian tablet (CTXT) on red blood cell (RBC) immune function in patients with oral lichen planus (OLP) for the sake of providing the basis of clinical medication. METHODS: Sixty patients with OLP were assigned randomly into three groups and were treated by CTXT, Tripterygium hypoglaucum tablet and polyactin-A tablet respectively. And the changes of RBC-C3b receptor and immune circulating rosette complex on the surface of erythrocytes (RBC-ICR) were measured by saccharomycetic assay. RESULTS: Effect of CTXT was superior to that of Tripterygium hypoglaucum and polyactin-A tablets. CONCLUSION: CTXT is a relatively effective remedy with less side effect, it is worthy to be studied further.

Adult↗

Effect of dietary fats on the fatty acid compositions of serum and immune tissues in chickens.

The purpose of the present study was to measure the effect of dietary fat source on the fatty acid composition of immune cells in chickens. One-day-old female chicks were fed corn and soybean meal-based diets containing 7% of either lard, corn oil, canola oil, linseed oil (LO), or menhaden fish oil (FO). After being fed experimental diets for 3 to 4 wk, samples of serum, thymus glands, bursa of Fabricius glands, and splenocytes were collected. All samples were frozen and stored at -80 C until lipid analysis. Results indicate that the fatty acid composition of the sera and immune tissues of chickens reflected the fat in the diet. The relative content of long-chain polyunsaturated fatty acids varied considerably among immune tissues, with, from greatest to least, spleen, bursa, and thymus. The young chick demonstrated a substantial capacity to elongate and desaturate linoleic (C18:2n-6) and alpha-linolenic acids (C18:3n-3). Feeding chicks fats rich in n-3 fatty acids (e.g., LO or FO) decreased significantly (P less than .05) the level of arachidonic acid (C20:4n-6) present in the serum and immune tissues by 50 to 75%. The levels of eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C20:6n-3) were substantially increased (P less than .05) by FO and LO feeding. However, LO, which is rich in C18:3n-3, was generally only one-half to one-quarter as effective as FO in elevating EPA and DHA levels in immune tissues. The implications for these changes in serum and immune tissue fatty acid profiles are discussed briefly.

Animals↗

Impaired interleukin-2 production by T-lymphocytes in polycythemia vera.

T-lymphocyte function was investigated in a group of eight patients with polycythemia vera (PV) and 13 normals. Responsiveness of T-cells to stimulation by mitogen was significantly impaired in the PV patients (p = .02). Analysis of immune cell subpopulation composition by assessment of cell surface phenotype did not reveal imbalances that could account for impaired T-cell proliferative ability in PV patients. Addition of recombinant human interleukin-1 to PV mononuclear cell cultures did not enhance proliferative ability. Addition of recombinant human interleukin-2 to cultures had no effect on maximum mitogen stimulation in normals but significantly improved responses in PV patients (p less than .02), correcting them to normal levels. Measurement of interleukin-2 production by stimulated cultured mononuclear cells confirmed subnormal IL-2 production by PV T-cells (p less than .00005). Impaired IL-2 production could conceivably contribute to the pathogenesis of PV by limiting the ability of IL-2-dependent cells to regulate hematopoiesis.

Humans↗

No relation of tuberculin reactivity with quantitative analysis of peripheral blood lymphocyte subsets in haemodialysis patients.

Anergic response to tuberculin (PPD) is well known in haemodialysis patients (HDp). This cross-sectional controlled study was conducted to analyse the correlation of PPD response with demographical features, nutritional parameters and the distribution of peripheral blood lymphocyte (PBL) subtypes. In this study 29 HDp (17 men, 12 women; mean age 30.9 +/- 9.5 years) and 13 controls (eight men, five women; mean age 29.2 +/- 6.4 years) were included. The mean time spent on dialysis was 20.5 +/- 17.4 months. The mean PPD response was lower in HDp than controls (7.5 +/- 8 mm vs. 15 +/- 4 mm, P = 0.001). Fourteen patients (48%) were PPD (-) (eight men, six women; mean age 34.1 +/- 11.1 years) and 15 were PPD (+) (normergic) (nine men, six women; mean age 26.8 +/- 3.4 years). No difference was observed between PPD (-) and (+) groups for age, sex and time spent on dialysis. As nutritional parameters, body mass index, serum albumin, creatinine and cholesterol levels were measured and no differences were found between controls and the PPD (-) and (+) groups. Absolute lymphocyte counts were lower in HDP compared to controls (1290 +/- 296 vs. 1570 +/- 307 cells ml-1; P = 0.01). PBL subtype percentages and absolute counts (CD3, CD4, CD8, CD4/CD8, HLADR+CD3+, CD16+56+, CD19) were also similar between PPD(-) and (+) HDp. It was concluded that PPD response cannot be predicted by the distribution of PBL subtypes. The most probable cause of this observation is regulation of PPD reactivity by in situ immune cells whose composition is not reflected in the distribution of PBL.

Cross-Sectional Studies↗