Effect of Ca-panthotenate on human granulocyte oxidative metabolism.

Activated granulocytes play an important role in propagation of the inflammatory response by production of reactive oxygen species and release of their granule content. Hyperactivation of these cells is suggested to result in deterioration of wound healing and, probably, increase of cicatrization. Pantothenic acid and its stable salt form, Ca-Panthotenate, were shown to significantly improve surgical wound healing. Therefore, in the present study the modulating effect of Ca-pantothenic acid to subsequent stimulation with a variety of stimuli was investigated on isolated human PMN using functional assay systems: Lucigenin-dependent chemiluminescence (CL), release of myeloperoxidase (MPO). Ca-Panthotenate significantly inhibited the CL response of PMN upon stimulation with the chemotactic petide f-met-leu-phe, the tumor promotor PMA, and the granulocyte activating cytokines GM-CSF and TNF alpha at a concentration range of 5 to 50 mM, but not upon stimulation with opsonized zymosan. Moreover, Ca-Panthotenate significantly inhibited the release of myeloperoxidase from PMN upon stimulation with f-met-leu-phe at a concentration of 5 mM. In contrast, Ca-Panthotenate did not directly activate PMN in the assay systems tested. These in vitro results support the concept of an anti-inflammatory action of Ca-Panthotenate in vivo.     

Polymorphonuclear leukocyte chemiluminescence response in HLA-B27 positive and negative arthritic patients

Summary The polymorphonuclear leukocyte (PMN) chemiluminescence (CL) response to opsonized zymosan reflecting the C3b/C3bi-receptor-mediated PMN respiratory burst activation was studied in 99 arthritic patients typed for the HLA-B27 antigen. The results indicate that the B27 antigen per se is not associated with disturbances in PMN CL response. However, the erythrocyte sedimentation rate showed a correlation with CL, suggesting that the activity of arthritic disease may affect the PMN CL response.     

Effect of murine malarial circulating immune complexes on the production of reactive oxygen species by peritoneal exudate cells of normal mice

Circulating immune complexes (CIC) isolated from sera of mice infected with Plasmodium berghei by precipitation with polyethylene glycol were examined for their ability to stimulate the production of reactive oxygen species by peritoneal exudate (PEC) of normal mice, using luminol-aided chemiluminescence (CL). CIC were found to be capable of stimulating the production of CL by normal mouse PEC. Weaker CL responses were observed when PEC were incubated with P. berghei soluble antigens. Normal mouse IgG and IgG1, IgG2b subclasses showed no effect on the stimulation of the production of CL. When normal mouse PEC were preincubated with CIC, their CL responses to opsonized zymosan were significantly depressed to 34% of the control level. The data suggest that CIC are capable of stimulating phagocytes to release reactive oxygen species and mediating pathological tissue damage.     

Production of oxygen free radicals by phagocytes in patients on hemodialysis

In order to elucidate the vulnerability to infection in patients on chronic hemodialysis, as one of the host defense mechanisms, the production of oxygen free radicals by phagocytes was studied in patients by luminol- or lucigenine-enhanced chemiluminescence (CL). Whole blood CL of the patients, in both luminol- or lucigenine-enhanced was significantly higher than that in healthy adults after stimulation by zymosan, PMA, and Staphylococcus aureus (S. aureus) 209 P. However, the CL response of the patients' polymorphonuclear neutrophils (PMNs) with the same stimuli was slightly lower than that in healthy adults. There were no differences in the levels of opsonins, such as complements and immunoglobulins, between the patients and healthy adults. It appears that any factor in the patients' serum enhances CL response, because of the PMN CL response after addition of patients' serum was higher than that after addition of healthy controls' serum, and the PMN CL response after the addition of patients' serum obtained after hemodialysis was higher than that before hemodialysis. The addition of erythrocytes to PMNs from healthy adults caused a reduction in the PMN CL response, but the addition of urea and creatinine had no effect. The CL response induced by microsphere-bound luminol (lumisphere), which makes possible the direct measurement of highly reactive oxygen within phagosomes, was studied in the patients and controls. The CL response in the patients was slightly lower than those in controls, but not significant. These results suggest that not only CL response of phagocytes but also other defense mechanisms should be studied further to make clear the vulnerability to infection in these patients. In addition, the effect of three antibiotics, cefbuperazone, cefminox and latamoxef on luminol-enhanced CL of whole blood was studied in healthy adults and the patients. After 3-hour exposure to those drugs at subinhibitory concentration (1/4 MIC), Klebsiella pneumoniae (K. pneumoniae) 163 treated by drugs induced higher CL response of whole blood than that by untreated bacteria in both healthy adults and the patients, and the peak time of the CL response induced by the drug-treated bacteria was shorter than that by untreated bacteria. This study suggests that the three drugs at sub-MIC work in partnership with host defense against infection due to K. pneumoniae even in patients on chronic hemodialysis.     

Effect of erythromycin on the generation of neutrophil chemiluminescence in vitro

In order to elucidate the therapeutic mechanisms of low dose-long term erythromycin (EM) therapy in patients with diffuse panbronchiolitis (DPB), the authors evaluated the effect of in vitro EM treatment on neutrophil (PMN) oxygen radicals production. EM has potent capacity to suppress PMN chemiluminescence (CL) induced by the N-formyl Met-leu-phe (FMLP), opsonized zymosan, and calcium ionophore A23187 stimulation. In marked contrast, phorbol myristate acetate (PMA)-induced PMN CL were much less affected by EM treatment. The suppressive activity of EM was dependent on the EM concentration and at a EM concentration of 25 micrograms/ml, FMLP-induced PMN CL were suppressed by 45.3 +/- 5.6% (n = 7), but PMA-induced CL were suppressed only marginally, 11.9 +/- 3.7% (n = 7). The onset of inhibitory activity of EM is rapid and at 5 min., 60.1% of the maximum suppression at 60 min. was observed. This EM-induced suppression was found to be reversible and dependent on the EM-pretreatment temperature since the suppressive activity of EM were observed only at 37 degrees C but not at 0 degrees C. These results suggest that actively transported intracellular EM exerts its suppressive activity by inhibiting the process of Ca++ transfer or Ca++ utilization by cells. In addition, these results were consistent with the concept that EM might act as an anti-inflammatory agent in chronic bacterial airway infections such as bronchiectasis and DPB where the PMN appear to play an important role in the generation of airway destruction.     

Increased Spontaneous Production and Generation of Superoxide Anion by Blood Neutrophils in Patients with Asthma

Spontaneous production and PMA- and opsonized zymosan- stimulated generation of superoxide anion by blood cells in asthmatic patients were compared with those in normal volunteers and chronic obstructive pulmonary disease (COPD) patients using a lucigenin-dependent chemiluminescence method. Superoxide anion generation by 100 μl of blood in patients with asthma and/or COPD was significantly greater than that in normal subjects [asthma: 5684 ± 253 chemiluminescence (CI); COPD: 4994 ± 240 CL; normal: 2543 ±213 CL]. This is consistent with the increased superoxide generation per leukocyte (PMN) in these patients (Asthma: 1.56 ± 0.08 CL/PMN; COPD: 1.31 ± 0.08 CL/PMN; normal: 0.83 ± 0.07 CL/PMN. However, spontaneous production of superoxide by individual PMNs was increased only in asthmatic patients, compared with that in normal subjects (Asthma: 0.14 ± 0.02 CL/PMN; COPD: 0.07 ± 0.01 CL/PMN; normal: 0.07 ± 0.01 CL/PMN. These results indicate that the respiratory burst is enhanced in both asthmatic patients and COPD patients, and that superoxide production by resting neutrophils is also increased in asthmatic patients, but not in COPD patients, compared with normal subjects.     

Opioid peptides rapidly stimulate superoxide production by human polymorphonuclear leukocytes and macrophages

Opioid peptides found in the general circulation can modulate several functions of phagocytic cells that are related to their microbicidal and cytotoxic activity. Since reactive oxygen species are crucial to these activities, the affect of opioid peptides on superoxide (O-2) generation was evaluated with the use of lucigenin-enhanced chemiluminesence (CL). beta-Endorphin and dynorphin stimulate the production of O-2 in human polymorphonuclear leukocytes (PMN) and peritoneal macrophages (PMO) at peptide concentrations that prevail systemically (10(-14)-10(-12)M). There is an inverse dose-response relation for PMN but not PMO. The effect is rapid and sustained in PMN (peak CL at 2-4 min, duration greater than 15 min), whereas it is rapid but brief in PMO (peak 1 min, duration less than 3 min). Naloxone inhibits CL responses by greater than 75% in both cell types.     

Human Neutrophil Functions Are Inhibited In Vitro by Clinically Relevant Ethanol Concentrations

Neutrophils [polymorphonuclear neutrophils (PMNs)] play a pivotal role in host defense in man. These defenses may be compromised, however, in alcohol users and abusers. We therefore evaluated the effect of ethanol levels (12.5 to 500 mg/dl), on key functions of human PMNs—chemotaxis and production of reactive oxygen species—and on changes in cytosolic-free calcium ([Ca²⁺]_i), a pivotal intracellular mechanism of PMN activation. Ethanol significantly inhibited chemotaxis as evaluated by formyl-methionyl-leucyl-phenylalanine (fMLP)-induced upregulation of surface adhesion molecules (CD11b), fMLP-induced PMN elongation was only inhibited by a very high ethanol concentration of 500 mg/dl. Production of reactive oxygen species by normal PMNs was assessed by either chemiluminescence (CL) for hypochlorous acid or ferricytochrome c reduction (FCR) for superoxide anions. For PMN stimulated by fMLP, ethanol inhibited CL but not FCR. For PMNs activated by phorbol myristate acetate, ethanol inhibited both CL and FCR. Ethanol did not alter baseline [Ca²⁺]_i, as assessed by videomicroscopy using the Ca²⁺-sensing fluorescent dye Fura-2-AM, but did significantly potentiate the increase in peak [Ca²⁺]_i, levels that occurs in response to stimulation by fMLP. Calcium channel blockers attenuated ethanol's inhibition of CL. Thus, acute in vitro ethanol, at clinically relevant concentrations, can inhibit several critical aspects of PMN functions. But, in PMNs, unlike neural cells, these inhibitory effects do not seem to be mediated by decreases in Ca²⁺ influx or in [Ca²⁺]_i.     

Human polymorphonuclear leukocyte phagocytosis of crystalline cholesterol,bilirubin, and calcium hydroxyapatitein vitro

We tested the hypothesis that human polymorphonuclear leukocytes (PMNs) phagocytize crystalline cholesterol, bilirubin, or calcium hydroxyapatitein vitro and in the process release oxygen metabolites and enzymes involved in the inflammatory process. Chemiluminescence (CL), elicited by the respiratory burst (release and activation of oxygen metabolites and enzymes) of PMNs during phagocytosis of a target particle, was used to quantitate PMN phagocytosis of each crystal. Significant CL (P<0.05) was observed with cholesterol concentrations of 1.3–5.3 mg/ml and the dose-response was linear (r≥0.95). With bilirubin, significant CL was observed with concentrations of 0.07–0.33 mg/ml. The response to calcium hydroxyapatite was variable. Human PMNs phagocytize cholesterol, bilirubin, and to a lesser extent, calcium hydroxyapatite. PMN chemiluminescence was associated with phagocytosis, indicating that inflammatory substances are being released in the process. These results support the concept that crystals that occur in the gallbladder may initiate gallbladder inflammation.     

Polymorphonuclear leukocyte-generated oxygen metabolites decrease beat frequency of human respiratory cilia

We investigated the effect of polymorphonuclear leukocyte (PMN)-generated oxygen metabolites on the ciliary beat frequency. PMNs were incubated with human respiratory cilia obtained by nasal brushing. The oxidative metabolism was stimulated by opsonized zymosan, and ciliary beat frequency was evaluated before and after activation of PMNs. Ciliary beat frequency was studied using video microscopy. Our results demonstrate a significant decrease in ciliary beat frequency after activation of PMNs. This effect was reduced by catalase. These data suggest that the PMN-generated oxygen metabolites, particulary H₂O₂, decrease beat frequency of human respiratory cilia. Offprints requests to: A. Kantar     

Oxygen free radical producing leukocytes cause functional depression of isolated rat hearts: role of leukotrienes

Polymorphonuclear granulocytes PMN) are suggested mediators of myocardial ischemia-reperfusion injury. We have previously shown that activated PMN producing oxygen free radicals (OFR) in the coronary circulation are cardiodepressive. OFR may induce lipid peroxidation and production of eicosanoids. We have investigated the influence of cyclo-oxygenase and lipoxygenase inhibitors on the effects of activated, OFR producing PMN in the Langedorff rat heart model. Left ventricular developed pressure (LVDP) was measured by a balloon in the left ventricle. Human PMN and drugs were given into the aortic cannula for 10 min and the hearts were observed for 30 min thereafter. After infusion for 5 min OFR production in the cellular infusate was measured at the level of the aortic cannula by a chemiluminescence (CL) technique. Phorbol 12-myristate 13-acetate (PMA)-activated PMN (n = 8), produced a CL response of 27649 +/- 11048 counts (mean +/- S.E.M.), and reduced coronary flow (CF) to 53 +/- 6% (mean +/- S.E.M.) and LVDP to 38 +/- 9% of baseline values at the end of the observation period. Ibuprofen (n = 6), a cyclooxygenase (CO) inhibitor, neither influenced the CL response (31915 +/- 7563) of activated PMN, nor the reduction of CF and LVDP at this time. Although both BW 755C (n = 7), a dual inhibitor of CO and lipoxygenase (LO) (CF:90 +/- 4%, LVDP:99 +/- 6%) and diethylcarbamazine (DCM) (n = 8), a LO inhibitor (CF:88 +/- 11%, LVDP:87 +/- 4%), significantly inhibited the cardiodepressive effects of activated PMN. BW 755C alone abolished the CL response (431 +/- 158 counts), whereas DCM had no effect on CL (30105 +/- 1698 counts).(ABSTRACT TRUNCATED AT 250 WORDS)     

The production of reactive oxygen species in mice infected or immunized with Plasmodium berghei

The capacity of peritoneal exudate cells (PEC) obtained from mice infected or immunized with Plasmodium berghei to produce reactive oxygen species (ROS) and the biological basis of this response was investigated, using luminol-dependent zymosan-triggered chemiluminescence (CL). CL response of PEC from infected mice increased at the early stage but was significantly depressed at the later course of the infection. A similar biphasic activity of peroxidase was also observed in PEC from infected mice. On the other hand, PEC from immunized mice exhibited concomitant increases of the ability to produce CL, the activity of peroxidase and the expression of Fc and C3 receptors on cell surface. Compared with the controls, PEC from immunized mice showed an elevated background CL, responded more rapidly to the stimulation and generated considerably higher CL when triggered with opsonized zymosan. The data suggest that phagocytes in immunized mice are active in the production of ROS while those in infected mice are less active, and the inhibition of the ability of phagocytes to produce ROS may be one of the mechanisms for the parasites to escape from host immune system.     

Functional impairment in isolated rat hearts induced by activated leukocytes: protective effect of oxygen free radical scavengers

Ischemia-reperfusion activates polymorphonuclear leukocytes (PMN). Depletion of PMN has been shown to reduce the size of experimental myocardial infarction. We have studied whether PMN activated by phorbol myristate acetate (PMA) would depress function of the isolated rat heart, and if this effect was mediated by oxygen free radicals (OFR). Cells and/or drugs were added to the perfusate into the aortic cannula for 10 min, followed by a 30 min recovery period. Oxygen free radicals formation was verified by chemiluminescence (CL). PMA-activated PMN (n = 13) caused CL response of 27,493 +/- 5113 counts (mean +/- S.E.M.) and reduced left ventricular developed pressure (LVDP) to 30 +/- 9% and coronary flow (CF) to 49 +/- 7% of the baseline value at the end of the observation period. Addition of super-oxide dismutase (SOD) and catalase (CAT) (n = 11) reduced the CL response to 5623 +/- 806 counts, but did not influence either LVDP (36 +/- 15%) or CF (51 +/- 18%). Addition of thiourea (TU) to the activated cell suspension (n = 8) further reduced the CL response (3663 +/- 474 counts), and LVDP was 86 +/- 5% and CF was 87 +/- 3%. When TU + SOD + CAT was mixed with PMN + PMA (n = 11), the CL was almost abolished (117 +/- 21 counts) and LVDP was 73 +/- 8% and CF was 94 +/- 6%. When CF was reduced (n = 7) alike the CF reduction in the hearts receiving PMA + PMA, LVDP was not significantly changed at the end of the observation period (75 +/- 6%). Unactivated PMN (n = 8) caused minor response of LVDP and CF, similar to PMN + PMA + TU and PMN + PMA + SOD + CAT + TU. PMA alone (n = 8) was cardiotoxic and caused changes similar to PMN + PMA. This effect was not inhibited by scavengers (n = 6). The supernatant of the PMN + PMA suspension (n = 7) did not impair cardiac function, suggesting that no free PMA was available after mixing with PMN. We conclude that activated PMN in the coronary circulation depressed cardiac function and increased vascular resistance due to OFR production.     

Effect of Hyperoxia on Superoxide Anion and Hydrogen Peroxide Production of Polymorphonuclear Leucocytes and Alveolar Macrophages

Hyperoxia activates superoxide dismutase (SOD) while inactivating catalase and glutathione peroxidase in polymorphonuclear leucocytes (PMN) and alveolar marcophages (AM) obtained from guinea-pigs exposed to 85% oxygen for 90 h. The influence of these altered enzyme activities on the rate of oxygen consumption and release of superoxide anion (O--2) and hydrogen peroxide (H2O2) was investigated. By 18 h O--2 released from resting PMN increased two-fold and remained elevated through the entire periods of the study, whereas H2O2 release and oxygen consumption at the same time points remained normal. At 66 h PMN phagocytizing opsonized zymosan particles released additional quantities of O--2 and H2O2 and consumed significantly more oxygen compared to the usual increase noted at earlier time points. Although oxygen consumption was almost two-fold higher in AM than PMN, phagocytizing AM released three-fold less O--2 and five-fold less H2O2 than did PMN. Furthermore, AM of animals exposed to hyperoxia no longer exhibited enhanced O--2 production upon exposure to opsonized zymosan. Hydrogen peroxide release progressively decreased at rest but progressively increased during phagocytosis of opsonized zymosan during the 90 h exposure to hyperoxia. No changes in oxygen consumption of AM occurred during hyperoxia. The divergent oxidative responses in PMN and AM of guinea-pigs exposed to hyperoxia suggest different biochemical adaptive mechanisms.     

Leukocyte and platelet function and eicosanoid production in subjects with hypercholesterolaemia

A group of 22 subjects with type IIA hypercholesterolaemia (mean serum cholesterol = 8.3 +/- 0.3 mmol/l) were sex, age and weight matched with 22 control subjects (mean serum cholesterol = 4.5 +/- 0.1 mmol/l). Diastolic blood pressure was significantly higher in hypercholesterolaemic subjects (79.2 +/- 1.4 mm Hg) than in control subjects (71.9 +/- 1.4 mm Hg). While the high cholesterol group had 52% greater thromboxane production in clotted whole blood than controls this difference was not significant, and the platelet aggregation and serotonin secretion response to doses of collagen, ADP and arachidonic acid were similar between the 2 groups. Polymorphonuclear leukocyte (PMN) chemiluminescence (used as a measure of reactive oxygen species production) in response to low doses of the chemotactic-peptide FMLP and opsonized zymosan was significantly greater in high cholesterol subjects compared to their matched controls. The production of platelet activating factor (PAF) by calcium ionophore (2.5 micrograms) stimulated PMN isolated from hypercholesterolaemic subjects (11.5 +/- 1.4 ng/10(6) cells) was significantly greater than PAF production by cells from the control group (8.3 +/- 1.0 ng/10(6) cells). Leukotriene B4 release by PMN in response to calcium ionophore did not differ between the 2 groups. These data suggest a degree of leukocyte activation in hypercholesterolaemic subjects compared to controls with normal cholesterol. In addition, plasma levels of lyso-PAF were higher in high cholesterol subjects (317 +/- 21 ng/ml) compared to their matched controls (271 +/- 18 ng/ml) perhaps indicating increased plasma acetylhydrolase activity in subjects with raised cholesterol levels. Recently described biological activity for lyso PAF suggests a possible role for this substance in atherogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neutrophil-endothelial cell interaction: evidence in vitro for a regulation by endothelial cells of neutrophil functions.

The purpose of this study was to investigate a possible relationship between human umbilical vein endothelial cells (EC) triggered by ionophore A23187 at different doses (0.5-2.5 microM) and polymorphonuclear neutrophils (PMN). EC supernatants were shown to contain neutrophil chemoattractant activity (NCA) and in parallel a factor inducing an inhibition of PMN chemiluminescence (PMN CL). Supernatants obtained from EC triggered by A23187 exhibited a high level of NCA (73 +/- 5 PMN.hpf-1 compared to 21 +/- 4 PMN.hpf-1 in untreated EC supernatants, p less than 0.01). This NCA was independent from arachidonic acid metabolites, since indomethacin and nordi-hydroguaiaretic acid failed to suppress the chemotactic activity. Using gel filtration chromatography (AcA 54) the NCA was recovered in a single peak of apparent molecular weight of 37,000 +/- 4,000 daltons. Checkerboard analysis indicated that NCA exhibited both chemotactic and chemokinetic activities. In addition, supernatants of A23187-stimulated EC, and at a lesser degree, supernatants of unstimulated EC, inhibited PMN CL induced by N-formyl-Methionyl-Leucyl-Phenylalanine (61% inhibition, p less than 0.05), and by A23187 itself (80% inhibition, p less than 0.01), but not that induced by phorbol-myristate-acetate. Indomethacin and protamine sulphate did not modulate this inhibitory activity. By contrast, EC-derived inhibitory activity was inhibited (50%) by an adenosine antagonist (8-phenyltheophylline), indicating a participation of adenosine in this inhibitory activity of PMN CL. These data suggest the possibility that activated endothelial cells could both enhance PMN migration and protect themselves against potential damaging effects of oxygen metabolites produced by PMN, particularly during transvascular migration.     

Role of serum in stimulation of polymorphonuclear leukocyte, luminol-dependent chemiluminescence by influenza A

Granulocyte membrane perturbation activates oxidative metabolism with the release of highly reactive species (O2-, H2O2, OH., and 'O2) and emission of light (chemiluminescence (CL)). Using the CL response as a measure of oxidative metabolism, we assayed the effects of influenza A on the granulocyte respiratory burst. Human polymorphonuclear leukocytes (PMNs) were isolated by Ficoll-Hypaque cushioning and dextran sedimentation. The isolated PMNs were incubated with egg-grown influenza A (H3N2) virus, or a medium control, in the presence of 1 microM luminol and fresh autologous serum (10%). No light emission occurred during the incubation of PMNs with the medium control. Influenza A (33 to 50% egg-infective-doses (EID50):1 PMN) stimulated PMN light emission with a maximal response (48,386 +/- 10,764 cpm/10(6) PMN) occurring at 37 degrees CL was dependent on the virus dose with a diminished response (6,041 +/- 3,200 cpm/10(6) PMN) occurring at a lower infectivity of 10 EID50:1 PMN. Chemiluminescence responses were similar with infective and with noninfective virus particles (heat inactivated, 56 degrees C X 2 h). Fresh serum was necessary for the influenza virus to cause a CL response. A significant correlation (p less than 0.01) existed between the level of light emission and the hemagglutination-inhibiting (HI) antibody titer to influenza A of the autologous serum. Virus in the absence of detectable antibody did not stimulate CL. The virus-associated CL was completely inhibited if autologous serum was heated (56 degrees C X 30 min) or if the PMNs were pretreated with cytochalasin B (5 mcg/ml X 5 min). These findings suggest that influenza A-associated PMN CL requires antibody, complement, and phagocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dose-dependent effects in the subacute response of the rat lung to quartz. II. Protease activities and levels of soluble hydroxyproline in lung lavage

The response of the rat lung to a range of doses of quartz at 50 and 100 days after its administration by intratracheal instillation has been assessed by bronchopulmonary lavage. The effects on the levels of protein and hydroxyproline and on the PZ peptidase and collagenolytic activities of lavage fluid supernatants are described and an assessment of the hydroxyproline content of recovered cells is made. In addition, assays for PZ peptidase and collagenase activity were carried out on polymorph enriched fractions and on samples obtained from short-term culture of recovered macrophages. Both protein and hydroxyproline measurements did show dependence on the amount of quartz instilled and the time after its administration. Measurements of PZ peptidase and collagenase activities suggest that the polymorphonuclear leukocytes, not the macrophages, are the major source of these degradative enzymes. The relevance of these findings with regard to the importance of the PMN in quartz-induced fibrosis, is discussed.     

Effects of r-metHuG-CSF on polymorphonuclear leucocyte kinetics and function in patients on continuous ambulatory peritoneal dialysis

End-stage renal failure (ESRF) patients undergoing continuous ambulatory peritoneal dialysis (CAPD) are immunocompromised and exhibit abnormal circulating polymorphonuclear leucocyte (PMN) function, including reduced phagocytosis and intracellular killing. Six uraemic patients on CAPD were each given 300 μg granulocyte-colony stimulating factor (G-CSF) every day for 5 d and PMN function tests were performed daily. By day 5 of the study CD11b expression was significantly decreased in response to N -formylmethionylleucylphenylalanine (fMLP) and opsonized Staphylococcus epidermidis stimulation, and expression of L-selectin (CD62L) was significantly decreased in response to opsonized Staphylococcus epidermidis stimulation. Further, superoxide anion production and FcγRI (CD64) expression were found to be significantly increased and FcγRIII (CD16) expression was lowered. Circulating white cell and PMN counts were significantly elevated in response to treatment. Administration of G-CSF did not appear to have corrected the abnormalities in phagocytosis and intracellular killing. This study suggests that G-CSF does no harm to ESRF patients and influences uraemic PMN function in a manner that is comparable to its effects on PMN in non-uraemic subjects.     

急性心肌梗死患者中性粒细胞氧化代谢改变及维生素C的干预作用

目的：评价急性心肌梗死（AMI）患中性粒细胞（polymorphonuclear,PMN)氧化代谢功能以及维生素C的抗氧化损伤作用。方法：60例AMI患被列入研究对象,随机分成两组：Ⅰ组（30例）;给予AMI的常规治疗;Ⅱ组（30例）;在常规治疗的基础上加用维生素C静脉滴注,每天3g连续应用7d后停药。在入院后及治疗第1,3,7,10天检测中性粒细胞化学发光（polymorphonuclear chemiluminescence,PMN-CL)参数,并行心电图检查,与AMI患年龄、性别匹配的健康人62例作为对照组（Ⅲ组）。结果AMI患PMN－CL各项参数显性高于健康对照组。在第3,7d,Ⅱ组其各项参数较Ⅰ组明显下降,在停用维生素C后3d仍较Ⅰ组明显下降（P分别＜0．05,0．01,0．001）,心电图ST段改善的积分明显高于Ⅰ组。结论：AMI患中性粒细胞产生大量的氧自由基,造成机体氧化损伤;静脉滴注维生素C能有效抑制AMI患中性粒细胞产生氧自由基,从而能减轻AMI患心肌的进一步坏死。