The effect of glutamine supplementation and physical exercise on neutrophil function

Glutamine is the most abundant free amino acid in the body. Its primary source is skeletal muscle, from where it is released into the bloodstream and transported to a variety of tissues. Several studies have shown that glutamine is important for rat and human neutrophil function and that these cells utilize glutamine at high rates. Physical exercise has also been shown to induce considerable changes in neutrophil metabolism and function. As neutrophils represent 50-60% of the total circulating leukocyte pool and play a key role in inflammation, both physical exercise and glutamine might be expected to regulate the inflammatory process. In this review, the changes in neutrophil function induced by physical exercise and glutamine supplementation are compared.     

In vitro effect of actinomycin D on human neutrophil function

The effect of actinomycin D (ACT-D) on human neutrophil chemotaxis, chemiluminescence (CL), superoxide (O2-) production, phagocytic uptake, and intracellular bacterial killing has been examined. The viability of the ACT-D-treated neutrophils was 98% even at a concentration of 10 micrograms/ml for 4 hr. Using fMLP as the chemotactic factor, depressed chemotaxis was demonstrated following ACT-D (1-10 micrograms/ml) pretreatment of neutrophils as compared with the non-treated controls. Similar ACT-D pretreatment produced the depressed responses in phorbol myristate acetate-induced CL and superoxide production by neutrophils. Moreover, using heat-inactivated human serum as an opsonin for Salmonella enteritidis (NCTC 6676), there was a significant difference in intracellular killing (P less than 0.01) but no difference in phagocytic uptake between ACT-D-treated and non-treated neutrophils. These studies indicate that ACT-D profoundly impairs both intracellular bacterial killing by human neutrophil through an effect on respiratory burst activity and directed cell migration of human neutrophils.     

The effects of adenosine agonists on human neutrophil function

Adenosine is a potent physiologic substance with a variety of biologic activities. Many of the effects of adenosine appear to be mediated by two populations of cell-surface adenosine receptors (A1 and A2). We have examined the effects of several adenosine receptor agonists on human neutrophils stimulated with the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP). The results indicate that both superoxide anion generation and degranulation (as assessed by lysozyme release) are inhibited. Inhibition correlated most strongly with A2 receptor affinity for both parameters and was reversible by the adenosine receptor antagonist 8-phenyltheophylline. Because toxic oxygen metabolites and degradative enzymes are implicated in a variety of inflammatory disorders, adenosine agonists may be useful probes to help expand our knowledge of the role of these mediators in human disease.     

The effect of lipocortin 1 on neutrophil deformability

Lipocortn 1 (Lc1) is an anti-inflammatory protein, which, given systemically, inhibits polymorphonuclear neutrophil (PMN) emigration from the circulation to sites of inflammation; delivery of Lc1 to the inflamed site is ineffective. We have examined the effect of Lc1 on changes in PMN deformability, and observed a consistent improvement in the deformability of unstimulated PMN; N-formyl-methionyl-leucyl-phenylalanine (fMLP)-activated cell deformability was unaltered. A Lc1-induced increase in cell deformability may reduce PMN sequestration so contributing to the anti-migratory effects of systemic Lc1 previously demonstrated in vivo.     

The effect of hydrocortisone on neutrophil functional activity

The male (CBA X C57BL) FI mice received 125 mg of hydrocortisone per kg body weight intraperitoneally. The functional activity of neutrophils has been evaluated by means of nitroblue terazolium test (NBT-test) values taken before or after heat-killed S. marcescens cell stimulation in vitro by 2, 12, 24 h 3, 7 or 14 days post hormonal treatment. Throughout the 1st day after hydrocortisone administration the NBT-test values taken prior to as well as post microbial neutrophil stimulation were steadily increased. This effect could be seen as early as 2 h post hormone administration and it was linked with growing leukopenia and total decrease of blood granulocyte content. By the 3rd day the same very values turned up to become normal. The NBT-test values after microbial stimulation of neutrophils were 1.7 or 2.4 lower after hydrocortisone had been added to blood in vitro in a dose 3.5 X 10(-6) M or 7 X 10(-5) M.     

The effect of neutrophil migration on epithelial permeability

To reach an inflammatory lesion, neutrophils must frequently traverse the epithelium of an infected organ. Whether the actual migration of neutrophils alters the epithelial permeability is unknown. Through the use of an in vitro model system it was possible to directly determine the effect of neutrophil emigration on the transepithelial electrical resistance of the monolayer. Human neutrophils (5 X 10(6) cells/ml) were placed in the upper compartment of a combined chemotaxis/resistance chamber and stimulated for 40 min by a gradient of 10(-7) M n-formyl-methionyl-leucyl-phenylalanine to traverse a confluent monolayer of canine kidney epithelial cells grown on micropore filters. Neither the chemoattractant alone (10(-5)-10(-9) M) nor the accumulation of an average of eight neutrophils per millimeter of epithelium lowered the transepithelial electrical resistance. However, under certain conditions the migration of neutrophils temporarily increased the permeability of the monolayer. The resistance fell approximately 48% within 5 min if the migratory cells were stimulated to reverse their migration across the same monolayer. As re- migration continued, the resistance returned to its initial levels within 60 min. Doubling the initial neutrophil concentration to 10 X 10(6) cells/ml resulted in the accumulation of an average of 66 neutrophils per millimeter of epithelium and an average fall in resistance of 46% (r = 0.98; P less than 0.001) in 40 min. If the resistance had fallen less than 45%, removal of the neutrophils remaining in the upper compartment resulted in a return of the transepithelial electrical resistance to its initial level within 65 min. However, when the fall was greater than 45%, the resistance only recovered to 23.5% of its initial levels within the same time frame. Thus, these results suggest that the integrity of an epithelium can, under certain conditions, be affected by the emigration of neutrophils, but that this effect is either completely or partially reversible within 65 min.     

被动吸烟对雌性卵巢功能的影响

目的:探讨被动吸烟对雌性Wistar大鼠卵巢结构和功能的影响。方法:雌性Wistar鼠32只,随机分为对照组和被动吸烟组,对照组在自然环境下饲养,吸烟组在自制的吸烟箱内被动吸烟3个月,吸烟三个月后,对两组分别进行秤重,然后处死。用测量仪器测量母鼠卵巢的大小、重量,并做光、电镜观察,免疫组织化学检测ER、PR、FSHR、LHR在卵巢中的表达,所得数据进行统计学处理。结果:吸烟三个月大鼠卵巢充血性囊性退变,皮质萎缩,卵泡颗粒细胞排列紊乱;生长卵泡的颗粒细胞松散变性,排列不整齐;卵泡数减少,成熟的卵母细胞数目明显减少;髓质血管收缩,减少;间质疏松。②电镜对照组可见多个卵泡细胞,细胞内有空白颗粒及高密度颗粒。吸烟组可见多个颗粒细胞层,内有增粗的内质网、核糖体;核周隙局部增宽,线粒体模糊;线粒体水样变、空泡样变,线粒体嵴断裂、模糊;内质网脱颗粒样变。与没有吸烟的正常大鼠B组比较,吸烟大鼠的ER、PR、FSHR、LHR减少(P<0.05)。结论:被动吸烟组雌性卵巢充血性囊性退变,皮质萎缩,卵泡颗粒细胞排列紊乱。     

The influence of blood glucose on neutrophil function in individuals without diabetes

We assessed the association of neutrophil function with glycated hemoglobin (HbA1c) levels in a Japanese general population. Participants were 809 males and females who were over 20 years old living in the Iwaki region in Aomori Prefecture located in northern Japan. Lifestyle parameters (smoking, alcohol consumption, and exercise habits), HbA1c and neutrophil function such as reactive oxygen species (ROS) production capability and phagocytic activity (PA) were measured. ROS production capability was measured before and after phagocytic stimulus to obtain basal ROS production and stimulated ROS production. Level of HbA1c had a positive correlation with basal ROS production (p=0.053), a negative correlation with stimulated ROS production (p=0.072) and PA (p=0.059) only in post‐menopausal groups, and not in pre‐menopausal groups. However, there were no correlations between levels of HbA1c and neutrophil functions in male. In conclusion, in the present study, despite the presence of diabetes, chronic hyperglycemia was found to cause an increase in daily basal ROS production of neutrophils, and increased susceptibility to infection caused by reduced neutrophilic reaction in females in their menopause. Therefore, from the oxidative point of view, strict glycemic control is necessary to prevent post‐menopausal females from developing diabetic complications in spite of the presence of diabetes.     

Effect of alcohol drinking and cigarette smoking on neutrophil functions in adults

In recent years, the effects of smoking and excessive alcohol consumption on immune function have been studied, due to a high prevalence of infection or cancer in heavy drinkers, and the combination of smoking and drinking was considered to be a carcinogenic risk. However, the effect of smoking and drinking on systemic immune function has yet to be clearly understood. In this study, we investigated neutrophil functions (reactive oxygen species (ROS) productive activity, phagocytic ability and serum opsonic activity) and their relationship with alcohol consumption or amount of smoking. In total there were 731 male and female adult subjects who participated in the Iwaki Health Promotion Project in 2005. Multiple regression analysis showed a trend of increased ROS production in male subjects and a statistically significant decrease was observed in phagocytic activity caused by smoking in female subjects. In other words, oxidative stress caused by smoking in male subjects may be involved in ROS production from neutrophils. Decreased phagocytic activity of neutrophils caused by smoking suggests that host defense functions were impaired in female subjects. A relationship between neutrophil functions and the amount of alcohol consumption was not observed. Copyright © 2011 John Wiley & Sons, Ltd.     

P-Rex1 regulates neutrophil function

Rac GTPases regulate cytoskeletal structure, gene expression, and reactive oxygen species (ROS) production. Rac2-deficient neutrophils cannot chemotax, produce ROS, or degranulate upon G protein-coupled receptor (GPCR) activation. Deficiency in PI3Kgamma, an upstream regulator of Rac, causes a similar phenotype. P-Rex1, a guanine-nucleotide exchange factor (GEF) for Rac, is believed to link GPCRs and PI3Kgamma to Rac-dependent neutrophil responses. We have investigated the functional importance of P-Rex1 by generating a P-Rex1(-/-) mouse. P-Rex1(-/-) mice are viable and healthy, with apparently normal leukocyte development, but with mild neutrophilia. In neutrophils from P-Rex1(-/-) mice, GPCR-dependent Rac2 activation is impaired, whereas Rac1 activation is less compromised. GPCR-dependent ROS formation is absent in lipopolysaccharide (LPS)-primed P-Rex1(-/-) neutrophils, but less affected in unprimed or TNFalpha-primed cells. Recruitment of P-Rex1(-/-) neutrophils to inflammatory sites is impaired. Surprisingly, chemotaxis of isolated neutrophils is only slightly reduced, with a mild defect in cell speed, but normal polarization and directionality. Secretion of azurophil granules is unaffected. In conclusion, P-Rex1 is an important regulator of neutrophil function by mediating a subset of Rac-dependent neutrophil responses. However, P-Rex1 is not an essential regulator of neutrophil chemotaxis and degranulation.     

The effect of Helicobacter pylori on neutrophil chemotaxis is independent of cagA

Sixteen Helicobacter pylori strains were studied in order to determine their neutrophil chemotactic activity and the association with the presence cagA gene. Neutrophil chemotactic activity was detected by a modified Boyden chamber method and the results were expressed in terms of chemotactic index (CI). The presence of cagA was determined by PCR. Of the 16 strains, eight were cagA+ and eight were cagA-. All of the isolated strains showed chemotactic activity. The mean value of CI of the patient group was significantly higher than the negative control (P < 0.01). The mean value of CI of zymosan-activated serum (P < 0.05) and the reference strain H. pylori NCTC 11637 (HP11637) (P < 0.01) was significantly higher than the patient group's mean value of CI. There were no statistical significance in the CI between cagA+ and cagA- strains (P > 0.05). It is concluded that H. pylori attracts neutrophils by chemotaxis, however, there is no association with cagA.     

The effect of two bisphosphonates on human neutrophil chemiluminescence and myeloperoxidase activity

In order to assess the importance of chlorine in a drug molecule as an influence on myeloperoxidase-mediated inflammatory cell functions, the effect of the chlorinated bisphosphonate, clodronate, on human neutrophil chemiluminescence and myeloperoxidase (MPO) activity was compared to the non-chlorinated structural analogue, etidronate. The results suggested that the presence of chlorine may be important to the enhancement of MPO activity. In addition both drugs manifested low toxicity and both of these observations may have relevance to host defence.     

The effect of tobacco tax cuts on cigarette smoking in Canada

OBJECTIVE: To assess the effect of the tobacco tax cuts made in 1994 on the smoking habits of Canadians. DESIGN: Population-based retrospective cohort study. DATA: Data from the Survey on Smoking in Canada conducted by Statistics Canada on 11,119 respondents 15 years of age and older, who were interviewed about their smoking habits on 4 occasions, approximately every 3 months from January 1994 to February 1995. OUTCOME MEASURES: Changes in smoking prevalence, incidence, quit rates and mean number of cigarettes smoked per day in the provinces where tobacco taxes were cut and in those where taxes were not cut. RESULTS: During the survey, smoking prevalence decreased in all provinces, whether or not cigarette taxes had been cut. However, the prevalence of smoking was greater in the provinces where tobacco taxes had been cut than in those where they had not, and this difference increased from 2.0% at the beginning of the survey to 3.4% by the end (p < 0.001). In addition, rates of starting cigarette smoking were higher and smoking quit rates were lower in the provinces where taxes had been cut than in those where taxes had not been cut. CONCLUSION: Although smoking rates are declining in Canada, tobacco tax cuts appear to have slowed the rate of decline by inducing more nonsmokers to take up smoking and leading fewer smokers to quit.     

The effect of the laser microirradiation of the cell center on neutrophil motility

The cell center of human neutrophils spread on polylysine-coated coverslips was irradiated with an argon laser microbeam. After the cells were pretreated with acridine orange, the irradiation of the cell center in a dose of over 0.1 J completely and irreversibly suppressed the motility of neutrophils (both random migration and chemotaxis), even though the cells retained their polarization. The same dose, applied to the cell nucleus and the forward and backward edges of the cytoplasm, resulted in little, if any, effect on cell motility, and did not inhibit their movement toward the target. Electron microscopy of the cells with the irradiated center showed the microtubules to persist for no less than 30 minutes; no visible destruction was caused in the cell center structure. Consequently, the cell center directly controls (not through polymerization of microtubules) the motility of neutrophils.     

The effect of bedrest on adrenal function

Eight male subjects were subjected to continuous bedrest for 24–80 weeks for the purpose of studying metabolic responses. Three of the subjects did supine exercises daily during part of the study. Adrenal function was examined in relation to adrenal cortical and medullary excretions. The results reveal an increase in hydrocortisone throughout the test period, a decrease in norepinephrine and no change in epinephrine. These data suggest that exercise could decrease the severity of deconditioning caused by bedrest.     

The alterative effect of isobutylmethylxanthine in hypofunctional human neutrophil chemotaxis

The effects of isobutylmethylxanthine on the locomotion of chemotactically normofunctional and hypofunctional human neutrophils were compared. The hypofunctional cells were obtained from the peripheral blood of selected subjects with juvenile periodontitis. The chemically oriented migration (i.e. chemotaxis) of these cells was less than 50% of normal. Isobutylmethylxanthine caused a doubling of the CHO.Met.Leu.Phe.OH-induced chemotactic responsiveness of hypofunctional cells, while no effect of the drug was detected with respect to random migration. Isobutylmethylxanthine had no effect on chemotaxis or random migration in the normofunctional cell populations. Since isobutylmethylxanthine inhibits cAMP catabolism, these data suggest that the cyclic nucleotide plays a role in intracellular transduction mechanisms which affect chemotaxis.     

The effect of selenium sources and supplementation on neutrophil functions in dairy cows

Selenium (Se), an essential micronutrient, is believed to enhance neutrophil functions. This study aimed to compare the effects of supplemented organic (Sel-Plex®) and inorganic (sodium selenite) Se on neutrophil functions in high-producing dairy cows, during the periparturient period. Twenty-five Holstein cows were randomly allocated to five dietary treatments as follows: control diet (basal diet without Se supplementation), IN 0.3 (basal diet supplemented with inorganic Se at 0.3 mg/kg dry matter (DM)), IN 0.5 (inorganic Se at 0.5 mg/kg DM), OR 0.3 (organic Se at 0.3 mg/kg DM) and OR 0.5 (organic Se at 0.5 mg/kg DM). Some evaluated parameters included neutrophil functions and plasma Se concentrations in cows and plasma Se concentrations in calves. Neutrophil phagocytosis did not significantly differ among the five groups. However, organic Se supplementation significantly increased (P < 0.01) the respiratory burst of neutrophils when compared to cows fed IN 0.3 and the control diet. In comparison to inorganic Se, neutrophil apoptosis was decreased (P < 0.01) when cows were fed organic Se or the control diets. These effects of organic Se on respiratory burst activities and apoptosis of neutrophils were in a dose-dependent manner. Calf plasma Se concentrations were higher (P < 0.05) when cows were fed OR 0.5 and IN 0.5.