Effects of oxysterols upon macrophage and lymphocyte functions in vitro

Oxygenated derivatives of cholesterol (oxysterols), found in high concentrations in atherosclerotic lesions, are potent immunosuppressive agents inhibiting T-cell responses to different stimuli. The action of oxysterols on macrophage functions and macrophage-lymphocyte interaction has been poorly investigated. In this work, the effects of 25-hydroxycholesterol (25-OHCh) and 7-ketocholesterol (7-KCh) upon some functions of murine peritoneal macrophage (PM), such as generation of reactive oxygen intermediates (ROI), secretion of neopterin and interleukin-1 (IL-1)-like activity, Fc-receptor (FcR) activity, and murine and human lymphocyte functions, participating in lymphocyte-macrophage interactions, such as macrophage-activating factor (MAF) and Ia-inducing factor (IaIF) secretion, were studied in vitro. 7-KCh in concentration of 5 micrograms/mL culture medium only, but not 25-OHCh, significantly inhibited ROI generation by zymosan-stimulated PM. Pretreatment of PM for 22 h with 25-OHCh and 7-KCh led to the decrease of IL-1-like activity secretion. 25-OHCh and 7-KCh inhibited both FcR-dependent binding and phagocytosis of sheep red blood cells (SRBC). Oxysterols did not change both spontaneous and lipopolysaccharide-stimulated secretion of neopterin by PM. 25-OHCh dose-dependently and more efficiently than 7-KCh inhibited murine splenocyte secretion of MAF, which activity was determined by the ability of splenocyte-conditioned medium to stimulate ROI generation in PM. Both 25-OHCh and 7-KCh inhibited significantly proliferative activity of human mixed lymphocyte culture (MLC), as well as lymphocyte secretion of IaIF, which stimulates the expression of HLA antigens in cultured human monocytes. Purified Ch did not alter these parameters. These data showed, that some inflammatory functions of macrophages and lymphocytes may be modified by such environmental conditions as the presence of oxysterols.     

Pituitary adenylate cyclase-activating polypeptide (PACAP38) modulates lymphocyte and macrophage functions: stimulation of adherence and opposite effect on mobility

The effects of pituitary adenylate cyclase-activating polypeptide (PACAP38) in a concentration range from 10(-13) to 10(-6) M were studied, in vitro, on two functions of peritoneal rat lymphocytes and macrophages: adherence and mobility (spontaneous and chemotaxis). The results show that PACAP38 raised the adherence of the two cell types, increased the mobility of macrophages and decreased the mobility of lymphocytes. The maximal effects were observed at 10(-10) M in macrophages and at 10(-9) M in lymphocytes. Moreover, incubation with increasing concentrations of phorbol myristate acetate (PMA), a protein kinase C (PKC) activator, resulted in a progressive enhancement of adherence and chemotaxis of both macrophages and lymphocytes. In contrast, retinal, a PKC inhibitor, significantly decreased these capacities. Incubation of macrophages with both PMA and PACAP38 did not have a synergistic effect on chemotaxis and adherence whereas, with lymphocytes, adherence was increased and chemotaxis was partially decreased. On the other hand, incubation with forskolin (an enhancer of intracellular cyclic AMP [cAMP] levels) caused inhibition and stimulation of chemotaxis and adherence, respectively, in both cell types. PACAP38 prevented the inhibitory effect of forskolin on chemotaxis of macrophages but not of lymphocytes, whereas the simultaneous presence of PACAP38 and forskolin was synergistic for adherence of both peritoneal cells. In addition, PACAP38 was chemoattractant for macrophages but not for lymphocytes. Furthermore, a VIP receptor antagonist was able to partially reverse the modulatory effects of PACAP38 on lymphocytes, but not on macrophages. These data suggest that PACAP38 exerts its action through the binding to type I PACAP receptors and PKC activation in macrophages and through the elevation of intracellular cAMP levels by binding to type II PACAP receptors in lymphocytes. The present work reveals an additional link between neuropeptides and the immune system and suggests that the peptide PACAP modulates the immunological function of macrophages and lymphocytes.     

Profiles of chicken macrophage effector functions

In contrast to the mammalian system, avian species lack the so-called "resident" or "harvestable" macrophage population in the abdominal exudate. However, macrophages can be recruited into the chicken's abdominal cavity (presumably from the blood monocyte pool) if an inflammatory agent such as Sephadex is injected. The kinetics of inflammatory cell recruitment in terms of time, cell type, and state of activation to perform a particular effector function is currently an active area of research. This report will provide information on several chicken macrophage effector functions, including in vivo chemotaxis, phagocytosis, bacterial uptake and killing, biosynthesis of nitric oxide and various enzymes, and monokines such as interleukin-1 and granulocyte colony-stimulating factor.     

Intestinal epithelial cell regulation of macrophage and lymphocyte interleukin 10 expression

Patients with recurrent angina after coronary artery bypass graft surgery pose a problem. Stent implantation has been advocated in an effort to avoid repeat operation and to address the limitations of balloon angioplasty. Aim of the present study was to determine the in-hospital and long-term results of stent deployment in focal, de novo lesions of vein grafts. Thirty-five focal, de novo lesions of vein grafts in 31 patients were treated with stent deployment. Twenty-four patients (77%) had three vessels, 6 (20%) two vessels and 1 (3%) single vessel disease. Saphenous vein grafts aged 9.7 +/- 4.2 years (range 1-19 years). Twenty-two lesions (63%) were located within the body of the saphenous graft, 8 (23%) at the graft/coronary artery anastomosis and 5 (14%) at the aorta/graft anastomosis. The indications for stent deployment included: suboptimal result from balloon angioplasty (defined as > or = 50% post-angioplasty residual stenosis) in 29/35 lesions (83%); post-angioplasty coronary dissection with threatening occlusion in 4/35 (11%); abrupt closure in 2/35 (6%). Patients were screened for death, myocardial infarction, bypass surgery and repeat angioplasty during in-hospital stay and after a follow-up of 12 +/- 8 months. Even-free survival curve was constructed by the Kaplan-Meier method. Stent deployment was successful in all patients. One stent was deployed in 24/35 lesions (69%), half Palmaz-Schatz stent in 6/35 (17%) and 2 or more stents in 5/35 (14%). The balloon/vessel ratio resulted of 1.0 +/- 0.1 Minimal lumen diameter increased from 0.8 +/- 0.4 to 3.8 +/- 0.6 mm, with a mean gain of 1.8 +/- 0.6 mm (range 1.8-4.0 mm). During the in-hospital period 1 patient (3.2%) died and 1 (3.2%) had a non Q wave myocardial infarction. Therefore, the clinical success rate, was 94%. During the follow-up period, 2 patients died (6.9%), 2 (6.9%) developed a non Q wave myocardial infarction, 1 (3.4%) underwent bypass surgery and 3 (10.3%) underwent repeat angioplasty. The estimated 2-year event-free survival rate (free from myocardial infarction, repeat surgery and repeat angioplasty) was 62%. In conclusion, Palmaz-Schatz stent deployment in focal, de novo vein grafts presents a high rate of procedural success, a low rate of acute complications and good long-term results.     

Effects of lindane exposure on rainbow trout (Oncorhynchus mykiss) immunity. III. Effect on nonspecific immunity and B lymphocyte functions

The effect of the organochlorine insecticide lindane (gamma-hexachlorocyclohexane) was examined on some major immune functions of rainbow trout (Oncorhynchus mykiss) on the chemiluminescent response of pronephric cells (PMA-induced) in phagocytosis, on the proliferation of lymphocytes with B and T mitogens, and on the number of B lymphocytes analyzed by cytofluorometry. Two different methods of exposure were tried via food (first protocol) and via a single intraperitoneal injection (second protocol). After the oral contamination at a daily body dose of 1 mg/kg for 30 days, a decreased chemiluminescent response was observed with persisted for two more weeks and disappeared over 1.5 months. No effect was observed on lymphocyte proliferation and on the number of circulating B lymphocytes. In the second protocol lindane was administered intraperitoneally at 10, 50, or 100 mg/kg body wt. After 45 days the lymphocyte proliferation of B cells was depressed but not the T cell one. The B cells number in head kidney as measured by cytofluorometry was not significantly modified. Some nonspecific immunity parameters in sera were significantly modified.     

Effects of variations in the proportions of saturated, monounsaturated and polyunsaturated fatty acids in the rat diet on spleen lymphocyte functions

To obtain further information about the immunomodulatory effects of specific dietary fatty acids, weanling male rats were fed for 6 weeks on high-fat (178 g/kg) diets which differed according to the principal fatty acids present. The nine diets used differed in their contents of palmitic, oleic, linoleic and alpha-linolenic acids; as a result the total polyunsaturated fatty acid (PUFA) content and the PUFA:saturated fatty acid ratio varied (from 17.8 to 58.5 g/100 g fatty acids and from 0.28 to 5.56 respectively). The n-6 PUFA:n-3 PUFA ratio was kept constant in all diets at approximately 7.0. The fatty acid composition of the serum and of spleen lymphocytes were significantly influenced by that of the diet fed. The ex vivo proliferation of spleen lymphocytes decreased as the level of oleic acid in the diet increased. Spleen natural killer cell activity decreased as the oleic acid content of the diet increased and increased as the palmitic acid content of the diet increased. The extent of the effects of these fatty acids on lymphocyte functions was modified by the nature of the background fatty acid composition of the diet.     

Effects of vasopressin on human memory functions

Arginine vasopressin and a number of its synthetic analogs augment memory functions in experimental animals. One of these analogs, 1-desamino-8-D-arginine vasopressin (DDAVP), influences human learning and memory. Cognitively unimpaired, as well as cognitively impaired adults, treated with DDAVP for a period of several days, learn information more effectively, as measured by the completeness, organization, and consistency (reliability) of recall. DDAVP also appears to reverse partially the retrograde amnesia that follows electroconvulsive treatment.     

Effects of chicken anemia virus on macrophage function in chickens

One-day-old chicks were inoculated intramuscularly with chicken anemia virus (CAV). Four birds were killed at 7, 14, 21, 28, and 42 days postinoculation (PI), and macrophages were recovered from spleen and bone-marrow suspensions. These were tested for interleukin-1 (IL-1) production, Fc receptor expression, phagocytosis, and bactericidal activity. Macrophages recovered from uninoculated chickens at the same sample times, and exposed to CAV in vitro, were also tested. IL-1 production, Fc receptor expression, phagocytosis, and bactericidal activity were significantly lower in all macrophage cultures from CAV-inoculated chickens, and in cultures exposed to the virus in vitro, than in uninfected controls.     

Effects of Cryptosporidium parvum infection on lymphocyte phenotype and reactivity in calves

Cryptosporidium parvum is a protozoan parasite now recognized as a significant cause of neonatal diarrhea in calves, and infection is also widespread in both immunocompetent and immunocompromised humans. No effective treatment or preventive measures against C. parvum infection are available, owing largely to the lack of understanding of immunologic mechanisms of resistance to and recovery from this parasite. In the present study, we compared phenotypes of lymphocytes from peripheral blood, spleen, mesenteric, and prescapular lymph nodes of calves infected or not infected with C. parvum. We also compared reactivity of these lymphocytes to mitogens and C. parvum antigen in vitro. There were more non-T, non-B (null) lymphocytes in all tissues of infected compared with control calves. The percent of CD8+ lymphocytes was significantly increased in spleens of infected compared with control calves, and there were markedly less CD4+ than CD8+ cells in spleens of both groups (i.e. low CD4/CD8 ratios). Splenic lymphocytes showed significantly decreased in vitro proliferation to pokeweed mitogen and C. parvum antigen stimulation compared with lymphocytes from other tissues. These findings suggest that null lymphocytes and CD8+ lymphocytes may be important in the expression and regulation of bovine immune responses to C. parvum in vivo.     

Effects of lithium carbonate on memory and other cognitive functions

The authors studied the effects of lithium carbonate on memory and cognitive function in 16 psychiatric patients, who received lithium for 2 weeks and placebo for 2 weeks in a double-blind cross-over design. At the end of each treatment phase, subjects were administered a battery of memory and cognitive tests. As reported previously, lithium induced slowing of performance on certain of the perceptual motor tests; however, lithium did not cause memory impairment or a change in self-assessment of memory functions.     

Effects of gentamicin on rat submandibulary gland functions

1. Submandibular saliva was collected from anesthetized gentamicin-treated and control rats using carbachol, isoproterenol and pilocarpine as secretagogue. 2. Intraperitoneal injection of a large single dose (80 mg/kg) of gentamicin caused marked changes in saliva flow rate, protein and electrolyte concentrations in the presence of parasympathetic or sympathetic agents used as stimulants. 3. The secretion of N-acetyl-beta-D-glucosaminidase in saliva was determined and there was a marked increase in the enzyme activity of saliva of gentamicin-treated rats in comparison to that of controls. 4. The results of this study suggest that gentamicin as an aminoglycoside antibiotic at the dose employed, can influence the secretory mechanisms of rat submandibular glands.     

Effects of cisplatin on testicular functions in rats

Reflexes evoked by applying non-painful taps to an incisor tooth were recorded bilaterally from the jaw-closing masseter and temporal muscles of 21 humans. A series of inhibitory, excitatory, inhibitory and excitatory waves (the Q, R, S and T waves) appeared in full-wave rectified and averaged post-stimulus electromyograms. These reflex responses were affected by the participants' levels of attention. When they undertook mental exercises in the form of arithmetic calculations, increases in electro-myographic activity were found around the transitions between the Q and R and the S and T waves. These increases involved principally a shortening of the inhibitory Q and S waves. There was no significant difference between the occurrence of these effects in the QR and ST segments. However, the effects were seen more commonly when the reflexes were evoked by hard (7.4 mN.s) as opposed to soft (3.4 mN.s) taps. It is concluded that, in man, attentional factors can modulate both short- and long-latency jaw reflexes, particularly when these are evoked by higher-threshold afferent nerves.     

Protein kinase C-alpha modulates lipopolysaccharide-induced functions in a murine macrophage cell line

Lipopolysaccharide (LPS), a potent modulator of macrophage functional activity, binds to CD14 and triggers the activation of several protein kinases, leading to the secretion of variety of immunomodulatory molecules such as nitric oxide and proinflammatory cytokines. In this study, we have examined the role of the alpha isoenzyme of protein kinase C (PKC) in the regulation of LPS-initiated signal transduction in macrophages. To this end, we have stably overexpressed a dominant-negative (DN) version of PKC-alpha (DN PKC-alpha) in the murine macrophage cell line RAW 264. 7. Clones overexpressing DN PKC-alpha were indistinguishable from the parental line with respect to morphology and growth characteristics. At the functional level, DN PKC-alpha overexpression strongly inhibited LPS-induced interleukin-1alpha mRNA accumulation, and to a lesser extent inducible nitric oxide synthase and tumor necrosis factor-alpha expression. DN-PKC-alpha overexpression did not cause a general unresponsiveness to LPS, as secretion of the matrix metalloproteinase-9 was up-regulated in our DN PKC-alpha-overexpressing clones. Moreover, LPS-induced phosphorylation and degradation of IkappaBalpha, NF-kappaB activation, as well as p38 mitogen-activated protein kinase and Jun N-terminal kinase phosphorylation, were not affected by DN PKC-alpha overexpression. Collectively, these data provide evidence that PKC-alpha regulates selective LPS-induced macrophage functions involved in host defense and inflammation.     

Rat natural killer cell, T cell and macrophage functions after intracerebroventricular injection of SNC 80

We investigated the effects of (+)-4-[(alpha R)-alpha-((2S, 5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N, N-diethylbenzamide (SNC 80), a nonpeptidic delta-opioid receptor-selective agonist, on rat leukocyte functions. Intracerebroventricular injection of SNC 80 (20 nmol) in Fischer 344N male rats did not affect splenic natural killer cell activity compared with intracerebroventricular saline-injected controls. SNC 80 also had no effect on concanavalin A-, anti-T cell receptor-, interleukin-2- and anti-T cell receptor + interleukin-2-induced splenic and thymic lymphocyte proliferation in most experiments. In some experiments, however, SNC 80 significantly (P < .01) caused a 41 to 93% increase of concanavalin A-, anti-T cell receptor-, interleukin-2- and anti-T cell receptor + interleukin-2-induced splenic lymphocyte proliferation compared to controls. Additionally, SNC 80 did not significantly affect splenic T cell or natural killer cell populations as measured by the expression of T cell receptoralphabeta, and T helper (CD4), T suppressor/cytotoxic (CD8) and natural killer cell surface markers. Finally, SNC 80 did not affect interferon-gamma- or lipopolysaccharide (LPS)-induced splenic nitric oxide, and LPS-induced tumor necrosis factor-alpha production by splenic macrophages. These results suggest that SNC 80 could be useful in the treatment of pain without suppressing immune function. However, the potential immunoenhancing properties of SNC 80 may be also valuable in immunocompromised individuals.     

Effects of fatigue and anxiety on certain psychomotor and visual functions.

The comparative value of five measures of behavior decrement (steadiness, body sway, body sway time score, tapping rate, and critical flicker frequency) under conditions of fatigue or anxiety was studied in the collegiate competitive boxing situation. Measurements were made of 24 boxers under 4 conditions: at rest, after heavy exercise, before fighting, and after fighting. The data were subjected to analysis of variance. Measures of steadiness (hand steadiness and body sway) best satisfied the criteria for indicators of behavior decrement. "The remaining variables… may be made into more useful measures… if trial-to-trial variation and the very wide individual differences exhibited are diminished. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of deep saturation diving on the lymphocyte subsets of healthy divers

We examined the effect of deep saturation diving on the host defense mechanisms of five healthy volunteers using fluorescein-dye-conjugated monoclonal antibodies. Six divers engaged in a 440-m saturation diving simulation with total hyperbaric exposure of 30 days; five served as subjects. Change in the expression of surface molecules on the lymphocytes was analyzed during that period. Blood samples were serially taken on Days 4, 6, 8, 15, 22, 29, and after surfacing. The total number of lymphocytes showed no remarkable change. However, the fraction of T (CD3+) cells decreased from 68.0 +/- 3.3% to 55.8 +/- 5.8% (Day 8), and B cells increased reciprocally. In these T cells, the CD4:CD8 ratio (normally > 1.0) became less than 1.0 during compression and thereafter. In spite of the prophylactic use of anti-external otitis agents, one of the divers revealed a remarkable growth of Pseudomonas in the external auditory meatus, showing a high level of blood endotoxin (10.2 pg/ml). These results suggest that decrease in CD4+ fraction of T lymphocytes might explain in part the decreased resistance of divers to infective microorganisms in deep saturation diving.     

Effects of chronic alcohol use and age on human lymphocyte protein kinase C activity

The effects of alcohol exposure on human peripheral circulating lymphocyte protein kinase C (PKC) activity were characterized in lymphocytes harvested from two sample groups. The first group (control) consisted of 30 nonalcoholic male subjects and the second group consisted of nine male subjects with chronic alcoholism. Alcoholic subjects were admitted for detoxification to a substance abuse unit located in a nonprofit community hospital. In this group of subjects, blood was sampled on admission for detoxification (pre-A), and after 5 days (post-A). Subjects received chlordiazepoxide for treatment of alcohol withdrawal symptoms. PKC activities measured in the control, pre-A, and post-A groups expressed as pmol/microgram/min +/- SEM were 5.09 +/- 0.50, 1.81 +/- 0.43, and 3.95 +/- 0.44. Control PKC was significantly higher than pre-A PKC (p < or = 0.05) and post-A PKC was significantly higher than pre-A PKC (p < or = 0.05). Total lymphocyte PKC activity was also found to be inversely related to age, expressed by the relationship log(PKC) = 0.870-0.005(Age), with R = 0.433.     

Effects of human immunodeficiency virus sera and macrophage supernatants on mesangial cell proliferation and matrix synthesis

Patients with human immunodeficiency virus (HIV) infection are prone to the development of focal segmental glomerulosclerosis, a lesion in which increased mesangial cell proliferation and matrix synthesis may play a role. We undertook the present study to determine whether HIV sera may affect mesangial cell proliferation and matrix synthesis either directly or indirectly via effects on macrophage supernatants. Pooled HIV sera was found to significantly enhance (P < 0.01) mesangial cell proliferation in a concentration-related manner. Mesangial cell proliferation was significantly suppressed by two medications commonly utilized in HIV-infected patients, azidothymidine and trimethoprim/sulfamethoxazole, and was not significantly altered by lipopolysaccharide, suggesting that these medications as well as recurrent infection are unlikely to account for the proliferative effect of HIV sera. Supernatants from HIV sera-treated macrophages were found to significantly enhance (P < 0.01) mesangial cell incorporation of [3H]proline, a marker for synthesis of the matrix component collagen, compared to supernatants from control sera-treated macrophages. These results suggest that HIV sera may directly enhance mesangial cell proliferation and may indirectly increase mesangial cell matrix synthesis by altering macrophage secretory products. These effects may play a role in the development of glomerulosclerosis in patients with HIV infection.