1.Enhanced neutrophil functions by recombinant human granulocyte colony-stimulating factor in diabetic patients with foot infections in vitro.
Kyong Ran PECK ; Dong Woo SON ; Jae Hoon SONG ; Sungmin KIM ; Myoung Don OH ; Kang Won CHOE
Journal of Korean Medical Science 2001;16(1):39-44
This study was performed to evaluate the effect of granulocyte-colony stimulating factor on neutrophil functions in diabetic patients with active foot infections in vitro. Twelve diabetic patients with foot infections and 12 normal volunteers were enrolled. Neutrophils from peripheral blood were incubated with granulocyte colony-stimulating factor (G-CSF, 50 ng/mL) for 20 min. Superoxide production of neutrophils was measured by the reduction of ferricytochrome C. Neutrophil phagocytosis was assayed using Staphylococcus aureus and the weighted phagocytic index was calculated. Superoxide production of neutrophils in diabetic patients with foot infections was 7.7 (unit: nmol/2 x 10(5) cells/60 min), which was significantly lower than that in controls (12.0) (p<0.05). G-CSF increased neutrophil superoxide production to 12.1 in diabetic patients with foot infections and to 19.8 in controls (p<0.05 for each). Weighted phagocytic index in diabetic patients with foot infections was 0.77, which was not significantly different from that of the controls (0.69). Weighted phagocytic index was increased significantly by G-CSF to 0.88 in diabetic patients with foot infections and to 0.79 in controls (p<0.05 for each). In conclusion, G-CSF significantly enhanced neutrophil functions in diabetic patients with foot infections in vitro.
Adult
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Aged
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Bacterial Infections/immunology*
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Diabetes Mellitus/immunology*
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Female
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Foot Diseases/immunology*
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Granulocyte Colony Stimulating Factor, Recombinant/pharmacology*
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Human
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Male
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Middle Age
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Neutrophils/immunology
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Neutrophils/drug effects*
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Receptors, IgG/analysis
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Superoxides/metabolism
2.Effects of hydrocortisone on oxygen free radicals released by polymorphonuclear neutrophils in lipopolysaccharide-induced acute lung injury in mice.
Li ZHANG ; Kun-ling SHEN ; Tao ZHOU ; Yue-qiang XUE ; Peng YANG
Chinese Journal of Pediatrics 2004;42(9):659-662
BACKGROUNDCorticosteroid treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) has been one of the most controversial clinical issues in critical care. Although the administration of high-dose corticosteroids does not benefit patients with early septic shock and ARDS, recent clinical trials have indicated that treatment with relatively low-dose corticosteroids (2 to 3 mg/kg/day of methylprednisolone or equivalent) may improve outcome when used for late ARDS or persistent septic shock. The underlying mechanism was not fully clarified. Whether the administration of corticosteroids can arrest neutrophil-driven organ injury once started remains to be elucidated.
OBJECTIVETo observe the effects of hydrocortisone (HC, 6 mg/kg) on oxygen free radicals (OFR) released by PMN and pulmonary pathological changes in rat ALI model induced by lipopolysaccharide (LPS), to investigate the possible mechanism through which corticosteroids exert protective effect on ALI.
METHODSA rat model of ALI was induced by peritoneal injection of 2 x 10(12) Escherichia coli/kg. Fifty-six rats were randomly divided into three groups: normal control group, LPS group and HC group (6 mg/kg). Samples were collected 2 h, 4 h and 6 h after giving LPS to LPS and HC group (6 h after giving normal saline in normal control group) to measure the level of OFR released by PMN using chemiluminescence method based on lumino, and to compae of pulmonary pathological changes among the three groups.
RESULTSPathological examination with light microscope in LPS group showed thickened pulmonary interstitia, inflammatory cell infiltration, edema and hemorrhage, which were in accordance with the features of ALI. There were significant differences in the release of OFR by PMN among the three groups (P < 0.01). The level of OFR released by PMN in LPS group was significantly higher than that of the control group, and continued to increase during the observation period (2 - 6 h after LPS). The release of OFR by PMN in HC group was significantly suppressed as compared with LPS group, which was peaked at 4 h after LPS injection (to 98.2%); there were also significant differences in the grades of ALI pathologic changes among the three groups (P < 0.01). The grades of ALI pathologic changes in LPS group were significantly increased when compared with the normal control group (P < 0.05) while significantly decreased in HC group as compared with LPS group (P < 0.05).
CONCLUSIONIt was demonstrated in the LPS induced ALI model that OFR might play an important role in onset of ALI. Intervening with HC (6 mg/kg) treatment could ameliorate the lung injury and exert significant and sustained suppression on the release of OFR by PMN, showing that HC has a protective effect on LPS induced ALI and its theraputic effect occurs possibly through suppression on the release of OFR by PMN.
Acute Lung Injury ; etiology ; immunology ; Animals ; Disease Models, Animal ; Free Radicals ; metabolism ; Glucocorticoids ; pharmacology ; Hydrocortisone ; pharmacology ; Lipopolysaccharides ; adverse effects ; Lung ; immunology ; pathology ; Mice ; Neutrophils ; drug effects ; metabolism
3.The role of neutrophils in triptolide-induced liver injury.
Xin-Zhi WANG ; Shen-Ye ZHANG ; Yao XU ; Lu-Yong ZHANG ; Zhen-Zhou JIANG
Chinese Journal of Natural Medicines (English Ed.) 2018;16(9):653-664
Triptolide (TP) induces severe liver injury, but its hepatotoxicity mechanisms are still unclear. Inflammatory responses may be involved in the pathophysiology. Neutrophils are the first-line immune effectors for sterile and non-sterile inflammatory responses. Thus, the aim of the present study was to investigate the neutrophilic inflammatory response in TP-induced liver injury in C57BL/6 mice. Our results showed that neutrophils were recruited and accumulated in the liver, which was parallel to or slightly after the development of liver injury. Neutrophils induced release of myeloperoxidase and up-regulation of CD11b, which caused cytotoxicity and hepatocyte death. Hepatic expressions of CXL1, TNF-α, IL-6, and MCP1 were increased significantly to regulate neutrophils recruitment and activation. Up-regulation of toll like receptors 4 and 9 also facilitated neutrophils infiltration. Moreover, neutrophils depletion using an anti-Gr1 antibody showed mild protection against TP overdose. These results indicated that neutrophils accumulation might be the secondary response, not the cause of TP-induced liver injury. In conclusion, the inflammatory response including neutrophil infiltration may play a role in TP-induced hepatotoxicity, but may not be severe enough to cause additional liver injury.
Animals
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Chemical and Drug Induced Liver Injury
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etiology
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immunology
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Chemokine CCL2
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genetics
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immunology
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Diterpenes
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adverse effects
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Drugs, Chinese Herbal
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adverse effects
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Epoxy Compounds
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adverse effects
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Female
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Humans
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Interleukin-6
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genetics
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immunology
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Intracellular Signaling Peptides and Proteins
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genetics
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immunology
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Liver
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drug effects
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immunology
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Mice
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Mice, Inbred C57BL
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Neutrophil Infiltration
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drug effects
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Neutrophils
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drug effects
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immunology
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Phenanthrenes
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adverse effects
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Tripterygium
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adverse effects
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chemistry
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Tumor Necrosis Factor-alpha
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genetics
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immunology
4.Synthesis and evaluation of 2-cyano-3, 12-dioxooleana-1, 9(11)-en-28-oate-13β, 28-olide as a potent anti-inflammatory agent for intervention of LPS-induced acute lung injury.
Yi MOU ; Yan-Lin JIAN ; Tong CHEN ; Zhang-Jian HUANG ; Yi-Xue QIAO ; Si-Xun PENG ; Da-Yong ZHANG ; Hui JI ; Yi-Hua ZHANG
Chinese Journal of Natural Medicines (English Ed.) 2017;15(5):347-354
The present study was designed to synthesize 2-Cyano-3, 12-dioxooleana-1, 9(11)-en-28-oate-13β, 28-olide (1), a lactone derivative of oleanolic acid (OA) and evaluate its anti-inflammatory activity. Compound 1 significantly diminished nitric oxide (NO) production and down-regulated the mRNA expression of iNOS, COX-2, IL-6, IL-1β, and TNF-α in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Further in vivo studies in murine model of LPS-induced acute lung injury (ALI) showed that 1 possessed more potent protective effects than the well-known anti-inflammatory drug dexamethasone by inhibiting myeloperoxidase (MPO) activity, reducing total cells and neutrophils, and suppressing inflammatory cytokines expression, and thus ameliorating the histopathological conditions of the injured lung tissue. In conclusion, compound 1 could be developed as a promising anti-inflammatory agent for intervention of LPS-induced ALI.
Acute Lung Injury
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drug therapy
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genetics
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immunology
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Animals
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Anti-Inflammatory Agents
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administration & dosage
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chemical synthesis
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Bronchoalveolar Lavage Fluid
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immunology
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Cyclooxygenase 2
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genetics
;
immunology
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Female
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Humans
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Interleukin-1beta
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genetics
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immunology
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Interleukin-6
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genetics
;
immunology
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Lipopolysaccharides
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adverse effects
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Lung
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drug effects
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immunology
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Macrophages
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drug effects
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immunology
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Male
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Mice
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Mice, Inbred BALB C
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Neutrophils
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drug effects
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immunology
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Oleanolic Acid
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administration & dosage
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analogs & derivatives
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chemical synthesis
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Peroxidase
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genetics
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immunology
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RAW 264.7 Cells
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Tumor Necrosis Factor-alpha
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genetics
;
immunology
5.Effects of Huangqi injection on infection factors in children with acute lymphoblastic leukemia.
Xiao-Jia ZHANG ; Mei YAN ; Yu LIU ; Xue-Mei WANG ; Hailiqiguli NURIDING
Chinese Journal of Contemporary Pediatrics 2014;16(2):147-151
OBJECTIVETo investigate the effects of Huangqi injection on the infection factors in children with acute lymphoblastic leukemia (ALL) during remission induction chemotherapy.
METHODSNinety-one children with ALL were divided into treatment (n=47) and control groups (n=44) by a randomized double-blind method. During remission induction chemotherapy, the treatment group was given Huangqi injection (0.5 mL/kg·d) for 35 days, while an equal volume of normal saline was used instead in the control group; the other supportive care was the same for the two groups. After remission induction chemotherapy, the incidence of infection, duration of infection, white blood cell and neutrophil counts, site of infection, and positive rate of pathogenic bacteria in secretion were compared between the two groups.
RESULTSFour cases in the treatment group dropped out of the study due to allergic reaction. After remission induction chemotherapy, compared with the control group, the treatment group had a significantly lower incidence of infection (P<0.05), a shorter duration of infection at any site (P<0.05), a higher neutrophil count after chemotherapy (P<0.05), and lower incidence rates of respiratory tract infection, urinary tract infection, blood infection, and skin and soft tissue infections (P<0.05). Gram-negative bacteria were the main pathogens. Among the infected children, the positive rate of pathogenic bacteria in secretion was significantly lower in the treatment group than in the control group (P<0.05).
CONCLUSIONSHuangqi injection may reduce bone marrow suppression caused by chemotherapy drugs and increase neutrophil count during remission induction chemotherapy to reduce the incidence and duration of infection in children with ALL.
Adolescent ; Astragalus Plant ; adverse effects ; Child ; Child, Preschool ; Double-Blind Method ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; therapeutic use ; Female ; Humans ; Induction Chemotherapy ; adverse effects ; Infant ; Infection ; epidemiology ; Injections ; Male ; Neutrophils ; immunology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; immunology
6.Protectin D1 promotes resolution of inflammation in a murine model of lipopolysaccharide-induced acute lung injury via enhancing neutrophil apoptosis.
Xingwang LI ; Chunlai LI ; Wandong LIANG ; Yuntian BI ; Maohua CHEN ; Sheng DONG
Chinese Medical Journal 2014;127(5):810-814
BACKGROUNDProtectin D1 (PD1), derived from docosahexaenoic acid, has been shown to control and resolve inflammation in some experimental models of inflammatory disorders. We investigated the protective roles of protectin D1 in pulmonary inflammation and lung injury induced by lipopolysaccharide (LPS).
METHODSMice were randomly assigned to six groups (n = 6 per group): sham-vehicle group, sham-PD1 group, sham-zVAD-fmk group, LPS-vehicle group, LPS-PD1 group, and LPS-PD1-zVAD-fmk group. Mice were injected intratracheally with 3 mg/kg LPS or saline, followed 24 hours later by intravenous injection of 200 µg/mouse PD1 or vehicle. At the same time, some mice were also injected intraperitoneally with the pan-caspase inhibitor zVAD-fmk. Seventy-two hours after LPS challenge, samples of pulmonary tissue and bronchoalveolar lavage fluid were collected. Optical microscopy was used to examine pathological changes in lungs. Cellularity and protein concentration in bronchoalveolar lavage fluid were analyzed. Lung wet/dry ratios and myeloperoxidase activity were measured. Apoptosis of neutrophils in bronchoalveolar lavage fluid (BALF) was also evaluated by flow cytometry.
RESULTSIntratracheal instillation of LPS increased neutrophil counts, protein concentration in bronchoalveolar lavage fluid and myeloperoxidase activity, it induced lung histological injury and edema, and also suppressed apoptosis of neutrophils in BALF. Posttreatment with PD1 inhibited LPS-evoked changes in BALF neutrophil counts and protein concentration and lung myeloperoxidase activity, with the outcome of decreased pulmonary edema and histological injury. In addition, PD1 promoted apoptosis of neutrophils in BALF. The beneficial effects of PD1 were blocked by zVAD-fmk.
CONCLUSIONPosttreatment with PD1 enhances resolution of lung inflammation during LPS-induced acute lung injury by enhancing apoptosis in emigrated neutrophils, which is, at least in part, caspase-dependent.
Acute Lung Injury ; chemically induced ; drug therapy ; immunology ; Animals ; Apoptosis ; drug effects ; Docosahexaenoic Acids ; therapeutic use ; Inflammation ; drug therapy ; Lipopolysaccharides ; toxicity ; Male ; Mice ; Mice, Inbred BALB C ; Neutrophils ; cytology ; drug effects ; Peroxidase ; metabolism
7.Lysophosphatidylglycerol inhibits formyl peptide receptor like-1-stimulated chemotactic migration and IL-1beta production from human phagocytes.
Jae Woong SHIM ; Seong Ho JO ; Sang Doo KIM ; Ha Young LEE ; Jeanho YUN ; Yoe Sik BAE
Experimental & Molecular Medicine 2009;41(8):584-591
In this study, we observed that lysophosphatidylglycerol (LPG) completely inhibited a formyl peptide receptor like-1 (FPRL1) agonist (MMK-1)-stimulated chemotactic migration in human phagocytes, such as neutrophils and monocytes. LPG also dramatically inhibited IL-1beta production by another FPRL1 agonist serum amyloid A (SAA) in human phagocytes. However, LPG itself induced intracellular calcium increase and superoxide anion production in human phagocytes. Keeping in mind that phagocytes migration and IL-1beta production by FPRL1 are important for the induction of inflammatory response, our data suggest that LPG can be regarded as a useful material for the modulation of inflammatory response induced by FPRL1 activation.
Chemotaxis, Leukocyte/*drug effects
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Humans
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Interleukin-1beta/*biosynthesis
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Lysophospholipids/*pharmacology
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Monocytes/drug effects/immunology/metabolism/physiology
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Neutrophils/drug effects/immunology/metabolism/physiology
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Peptides/metabolism/pharmacology
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*Phagocytes/drug effects/immunology/metabolism/physiology
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Receptors, Formyl Peptide/*metabolism
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Receptors, Lipoxin/*metabolism
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Serum Amyloid A Protein/metabolism/pharmacology
8.Effect of the Combination of Xiyanping and Cefazolin on the Function of Neutrophils in Mice.
Nanyan XIONG ; Xueling WANG ; Xiaoxia LIU ; Jianhua CHEN ; Haiping ZHENG ; Zhongchao HUO ; Junfang JIAO
Journal of Biomedical Engineering 2015;32(5):1079-1082
Xiyanping is used to treat infectious diseases with antibiotics in clinic. The aim of this study is to investigate the mechanism of Xiyanping through studying the effect of the combination of Xiyanping with Cefazolin on the chemotaxis and phagocytic function of peripheral blood neutrophils in mice. Ten healthy mice were in control group. Forty healthy mice in experimental group were infected with staphylococcus aureus, and were randomly divided further into four groups, i. e. model group, Xiyanping group, Cefazolin group and combination group (Xiyanping with Cefazolin). Mice in the control group and model group were given normal saline (NS) through abdomen while those in other groups were given Xiyanping, Cefazolin, and Xiyanping with Cefazolin, respectively. The chemotaxis of peripheral blood neutrophils was detected with the transwell method, and the phagocytic function of peripheral blood neutrophils was analyzed with flow cytometry (FCM). In the present study, there was no significance on the chemotactic index of peripheral blood neutrophils in all the groups (P > 0.05). The actual phagocytotic rate and index of peripheral blood neutrophils in the blank group, Xiyanping group, and the combination group were significantly higher than those of the model group and Cefazolin group (P < 0.05). However, those were not significant in the blank group, Xiyanping group, and the combination group (P > 0.05) or between the model group and Cefazolin group (P> 0.05). Our results suggested the combination of Xiyanping and Cefazolin could enhance the therapeutic effect by improving the phagocytic function of peripheral blood neutrophils.
Animals
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Anti-Bacterial Agents
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pharmacology
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Cefazolin
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pharmacology
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Chemotaxis
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Disease Models, Animal
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Drugs, Chinese Herbal
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pharmacology
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Mice
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Neutrophils
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cytology
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drug effects
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Phagocytosis
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Staphylococcal Infections
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immunology
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Staphylococcus aureus
9.Reactive Cutaneous Cytophagocytosis in Nocardiosis.
Chi Yeon KIM ; Tae Heung KIM ; Won Sup LEE ; Ai Young LEE
Journal of Korean Medical Science 2002;17(2):279-282
Cutaneous nocardiosis, which usually manifests in the form of pustules, abscesses, or subcutaneous nodules, is occasionally found in immunocompromised patients. A 59-yr-old Korean man with myasthenia gravis and thymoma developed nodular skin lesions on his trunk. Histopathologically, abscess formation with a dense infiltrate of neutrophils and many cytophagic histiocytes were observed. Numerous filamentous organisms, which turned out to be Nocardia asteroides by culture, were also found. After sulfamethoxazole-trimethoprim therapy, all of the skin lesions rapidly decreased in size, with a marked diminution of the number of cytophagic histiocytes, and cleared up within four months. On reporting a case of cutaneous nocardiosis showing unusual histopathologic findings, we considered that reactive conditions should be included in the differential diagnosis of the cutaneous cytophagocytosis, and that nocardiosis could be one of the diseases showing reactive cytophagocytosis.
Anti-Bacterial Agents/therapeutic use
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Histiocytes/*immunology
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Humans
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Male
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Middle Aged
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Myasthenia Gravis/complications
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Neutrophils/*immunology
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Nocardia Infections/drug therapy/*immunology/microbiology/pathology
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Nocardia asteroides/drug effects/*immunology/isolation & purification
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Phagocytosis/*immunology
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Skin Diseases, Bacterial/drug therapy/*immunology/microbiology/pathology
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Thymoma/complications
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Thymus Neoplasms/complications
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Treatment Outcome
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Trimethoprim-Sulfamethoxazole Combination/therapeutic use
10.The role of C5a in adhesion properties of polymorphonuclear leukocyte to pulmonary vascular endothelial cells in burn patients with acute lung injury.
Fenglin LU ; Xihua ZHU ; Chengxiang HU ; Yunhui HUANG
Chinese Journal of Burns 2002;18(6):358-361
OBJECTIVETo explore the postburn adhesion properties of polymorphonuclear leukocyte (PMN) onto pulmonary vascular endothelial cells (PVEC) in burn patients with acute lung injury (ALI), so as to determine the role of C5a on PVEC-PMN adhesion.
METHODSMicrotubule sucking technique was employed to determine the PVEC-PMN adhesion. The myeloperoxidase (MPO) was also assayed to reflect the magnitude of PVEC-PMN adhesion.
RESULTSThe magnitude of PVEC-PMN adhesion increased and the adhesion force increased along with an increase in rh-C5a concentration. Simultaneously, the MPO activity was increased, which could be inhibited by anti-C5aR McAb in a concentration 1:104.
CONCLUSIONBoth C5a and C5aR participated in PVEC-PMN adhesion, which might be important in the pathogenesis of ALI.
Acute Disease ; Antibodies, Monoclonal ; pharmacology ; Antigens, CD ; immunology ; Burns ; blood ; complications ; Cell Adhesion ; drug effects ; Cells, Cultured ; Complement C5a ; pharmacology ; Dose-Response Relationship, Drug ; Endothelium, Vascular ; cytology ; drug effects ; Fetus ; Humans ; Lung ; Lung Diseases ; complications ; Neutrophils ; cytology ; drug effects ; enzymology ; Peroxidase ; antagonists & inhibitors ; drug effects ; metabolism ; Receptor, Anaphylatoxin C5a ; Receptors, Complement ; immunology