No abstract available.
Monokines* ; Neutrophil Activation* ; Neutrophils*

BACKGROUND: There have been few reports suggesting involvement of mast cell and neutrophil to induce bronchoconstriction in aspirin-sensitive asthrna. OBJECTIVE: To evaluate mast cell and neutrophil activation in pathogenesis of aspirin-sensitive asthma. MATERIAL AND METHOD: We observed changes of serum NCA and MPO levels during L-ASA bronchoprovocation test in 14 subjects with aspirin-sensitive asthma. RESULTS: Serum NCA was significantly increased at 30 min(p=0.01) after the inhalation of L-ASA and then, no significant changes were noted at 240 min (p=0.14). NCA was significantly higher in subjects with late asthmatic responses than in those without it (p=0.04). Serum MPO level tended to increase at 30 min with no statistical significance (p=0.08), and then it significantly decreased at 240 min (p=0.05). There was no significant correlation between serum NCA and MPO level (r=0.22, p=0.58). CONCLUSION: These results support the view that NCA derived from mast cell may contribute to neutrophil recruitment into the airway in aspirin-sensitive asthmatic patients.
Asthma ; Bronchoconstriction ; Humans ; Inhalation ; Mast Cells ; Neutrophil Activation ; Neutrophil Infiltration ; Neutrophils*

OBJECTIVETo investigate the influence of succinic acid on the apoptosis of polymorphonuclear neutrophil (PMN) in human peripheral blood, and to explore its role in infection.

METHODSPMNs were incubated in vitro, and its concentration was adjusted to 5 x 10(6)/mL. Then the cells were divided into normal control group and 5,10, 20, 30 mmol/L succinic acid groups according to different concentrations of succinic acid added into the medium. The supernatant of the cultures in each groups were collected to determine the superoxide content. 1 mL cell suspension was collected from 5, 20 mmol/L succinic acid groups before treatment and at 2, 4, 6, 8, 10 post-treatment hours (PTH) for the determination of caspase-3 activity and the apoptosis rate.

RESULTSThe content of superoxide in 5, 10, 20, 30 mmol/L succinic acid groups (0.437 +/- 0.056, 0.432 +/- 0.024, 0.395 +/- 0.049, 0.386 +/- 0.010) was significantly lower than that in control group (0.505 +/- 0.028, P < 0.05). The caspase-3 activity in each group increased along with the incubation time, but was in lower concentration in 5 mmol/L succinic acid group and in higher concentration in 20 mmol/L succinic acid group when compared with that in control group (P < 0.05). The apoptosis rate of PMN in control group was (6.1 +/- 1.1)% before incubation, and it reached (13.2 +/- 2.0)% at 2 PTH, and (27.7 +/- 3.7)% at 10 PTH. The apoptosis rate of PMN in 5 mmol/L succinic acid group was lower than that in control group except that at 4 PTH (P < 0.05). On the other hand, the apoptosis rate in 20 mmol/L succinic acid group (during 4-10 PTH) were obviously higher at each time points compared with the control group (P < 0.05).

CONCLUSIONLow concentration of succinic acid can suppress the apoptosis of PMN, while high concentration of succinic acid has an opposite effect. It is known that bacteria can produce succinic acid.

Apoptosis ; drug effects ; Cells, Cultured ; Humans ; Neutrophil Activation ; Neutrophils ; cytology ; drug effects ; Succinic Acid ; pharmacology

BACKGROUND: The common histopathology of Behget's disease is vasculitis associated with activation of neutrophils. The level of plasma elastase a 1 proteinase inhibitor (E a 1 PI), which represents the activation of neutrophils, may be a marker of Behcet's disease. OBJECTIVE: We examined the level of plasma elastase al proteinase inhibitor to evaluate the degree of neutrophil activation in Behcet's disease. METHOD: We measured plasma elastase a 1 proteinase inhibitor in 34 cases of untreated Behcet's disease patients and 30 cases of normal individuals by an enzyme immunoassay. We also studied the differences between the levels in two clinical types of Behcet's disease, the complete and incomplete type. RESULTS: The plasma level of elastase a 1 proteinase inhibitor was significantly higher in untreated Behcet's disease patients than in healthy controls. However, there was no significant difference between the levels in the two clinical types. CONCLUSION: These data suggest that the elevated level of plasma elastase a 1 proteinase inhibitor may reflect a state of chronic activation of neutrophils in Behcet's disease immunologically and further studies will be needed to evaluate the clinical status of Behcet's disease patients by measuring levels of plasma elastase a 1 proteinase inhibitor.
Humans ; Immunoenzyme Techniques ; Methods ; Neutrophil Activation ; Neutrophils ; Pancreatic Elastase ; Plasma* ; Vasculitis

BACKGROUND: Toluene diisocyanate (TDI) is the most prevalent agent to cause occupational asthma (OA) in Korea. The pathogenic mechanism of TDI-induced OA is still unclear. Involvement of both immunological and non-immunologicaI mechanisms have been suggested. OBJECTIVE: To evaluate a possible role of neutrophil in the development of TDI-asthma. OBJECT AND METHOD: Myeloperoxidase (MPO) as a neutrophil activation marker in both serum and induced sputum, and IL-8 in induced sputum were measured. Induced sputa and sera were collected from 15 TDI-induced OA patients (classified to group I) during TDI- bronchoprovocation test and were compared with those from 11 asthmatic subjects with negative TDI-bronchoprovocation test (group II). MPO levels were measured by radioimmunoassay, IL-8 levels, by enzyme linked immunosorbent assay and albumin levels, by nephelometry. Sputum MPO and IL-8 levels were presented as a ratio to albumin. RESULT: Serum MPO level tended to decrease during the TDI-bronchoprovocation test in two groups, but no statistical significance was reached (p>0.05). However, the ratios of MPO (the ratio of MPO level measured at 30 min to MPO level at baseline, and the ratio MPO level measured at 360 min to MPO baseline) in group I were significantly lower than group II (p=0.004, p=0.03 respectively). The IL-8/albumin and MPO/albumin levels in induced sputum from group I were significantly increased after the TDI-bronchprovocation test in comparison to the baseline value which was obtained before the bronchoprovocation test (p=0.0l, p=0.02 respectively). There was a significant correlation between the percent increase of IL-8/albumin and the MPO/albumin in induced sputum (r=0.89, p<0.05). CONCLUSION: These findings suggest a possible involvement of neutrophil in the development of bronchoconstiction after the TDI exposure, and IL-8 might contribute to neutrophil recruitment to airway mucosa. Further investigation will be needed to investigate mechanism of neutrophil activation in the pathogenesis af TDI-induced OA.
Asthma, Occupational* ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin-8 ; Korea ; Mucous Membrane ; Nephelometry and Turbidimetry ; Neutrophil Activation* ; Neutrophil Infiltration ; Neutrophils* ; Peroxidase ; Radioimmunoassay ; Sputum* ; Toluene 2,4-Diisocyanate

Angiostatin is derived from enzymatic degradation of plasminogen and it has endogenous anti-angiogenic properties. Although tumor cells, macrophages, platelets, and neutrophils generate high amount of angiostatin, its expression is increased in inflammatory conditions. Moreover, angiostatin binds to integrin alpha(v)beta(3), ATP synthase, and angiomotin, which expressed on neutrophils. Activated neutrophils are essential to innate immune response, but also cause tissue damage through production of reactive oxygen species (ROS) and increase lifespan. In this article, it suggests several mechanism of angiostatin as immune regulator for neutrophils in inflammatory conditions; complex with integrin alpha(v)beta(3) and F(1)F(0) ATP synthase on lipid raft, attenuate polarization, and ROS production. These data provide possible exploit of double-edged role of neutrophils in acute inflammatory pathologies to preserve beneficial effect and minimize tissue damage.
Adenosine Triphosphate ; Angiostatins* ; Apoptosis ; Immunity, Innate ; Integrin alphaVbeta3 ; Macrophages ; Neutrophil Activation* ; Neutrophils* ; Pathology ; Plasminogen ; Reactive Oxygen Species

Asthma ; physiopathology ; Humans ; Inflammation ; etiology ; Matrix Metalloproteinase 9 ; analysis ; physiology ; Neutrophil Activation ; Neutrophils ; physiology ; Transforming Growth Factor beta ; physiology

BACKGROUND: Oxidative stress and inflammation are important factors in the pathogenesis of diabetes and contribute to the development of diabetic complications. To understand the mechanisms that cause vascular complications in diabetes, we examined the effects of high glucose and/or free fatty acids on the production of superoxide from neutrophils and their role in endothelial cell damage. METHODS: Human neutrophils were incubated in the media containing 5.5 mM D-glucose, 30 mM D-glucose, 3 nM oleic acid, or 30 microM oleic acid for 1 hour to evaluate superoxide production through NAD(P)H oxidase activation. Human aortic endothelial cells were co-cultured with neutrophils exposed to high glucose and oleic acid. We then measured neutrophil adhesion to endothelial cells, neutrophil activation and superoxide production, neutrophil-mediated endothelial cell cytotoxicity and subunits of neutrophil NAD(P)H oxidase. RESULTS: After 1 hour of incubation with various concentrations of glucose and oleic acid, neutrophil adherence to high glucose and oleic acid-treated endothelial cells was significantly increased compared with adhesion to low glucose and oleic acid-treated endothelial cells. Incubation of neutrophils with glucose and free fatty acids increased superoxide production in a dose-dependent manner. High glucose and oleic acid treatment significantly increased expression of the membrane components of NAD(P)H oxidase of neutrophil (gp91(phox)). Endothelial cells co-cultured with neutrophils exposed to high glucose and oleic acid showed increased cytolysis, which could be prevented by an antioxidant, N-acetylcysteine. CONCLUSION: These results suggest that high glucose and/orfree fatty acidsincrease injury of endothelial cells via stimulating NAD(P)H oxidase-induced superoxide production from neutrophils.
Acetylcysteine ; Diabetes Complications ; Endothelial Cells ; Fatty Acids, Nonesterified ; Glucose ; Humans ; Inflammation ; Membranes ; NADPH Oxidase ; Neutrophil Activation ; Neutrophils ; Oleic Acid ; Oxidative Stress ; Superoxides

OBJECTIVETo investigate the effects of advanced glycation end products (AGE) on the biological behavior of neutrophils in vitro, to look for the relationship between accumulation of AGE and abnormal inflammation in wound healing in diabetic mellitus patients.

METHODSNeutrophils were isolated from SD rats and incubated in vitro. The cells were divided into four groups according to different concentrations of AGE in cell suspension: control group (C, with treatment of RPMI - 1640), A group (with treatment of 0.315 mg/mL AGE + RPMI - 1640), B group (with treatment of 0.625 mg/mL AGE + RPMI - 1640), D group (with treatment of 1.250 mg/mL AGE + RPMI - 1640). Activity of neutrophils were determined by MTT colorimetric assay. Selectin-L mRNA expressions were analyzed by reversible transcription polymerase chain reaction (RT -PCR) technique. The levels of reactive oxygen species (ROS) in neutrophils were measured with DCFH-DA method. The protein concentration of neutrophil elastase (NE) was assayed by ELISA.

RESULTSThe activity of neutrophils were obviously increased in A, B, and D groups when compared with that in C group [(0.170 +/- 0.040) in C group, (0.320 +/- 0.030) in A group, (0.380 +/- 0.020) in B group, (0.290 +/- 0.010) in D group, P <0. 05]. The expression of Selectin-L mRNA in A, B, D groups were significantly higher than that in C group (0.95 +/- 0.08, 1.36 +/- 0.27, 0.50 +/- 0.26.vs.0.36 +/- 0.26, P < 0.05. respectively). The ROS levels in A, B, D groups was markedly higher than that in C group (1.64 +/- 0.20, 2.16 +/- 0.26, 3.26 +/- 0.75. vs. 0.72 +/- 0.15, P <0.05, respectively). The levels of NE in A, B, D groups were significantly increased when compared with that in C group(1.98 +/- 0.43, 2.50 +/- 0.43, 2.01 +/- 0.18 vs 0.91 +/- 0. 21, P <0.05, respectively).

CONCLUSIONAGE can enhance the activity of neutrophil, with change in cellular biological behaviors, which may be one of main reasons for abnormal inflammation in wounds of diabetes mellitus patients.

Animals ; Cells, Cultured ; Glycation End Products, Advanced ; metabolism ; pharmacology ; L-Selectin ; metabolism ; Leukocyte Elastase ; metabolism ; Male ; Neutrophil Activation ; Neutrophils ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism

OBJECTIVETo investigate the relationship between phospholipase D (PLD) activation and neutrophil priming induced by cardiopulmonary bypass (CPB), and try to clarify whether CPB-induced systemic inflammatory response can be attenuated by inhibiting neutrophilic PLD activation.

METHODSNeutrophils were isolated from arterial blood of 8 patients undergoing valve replacement before operation and 30 min after initiation of CPB respectively. Both the preoperative and CPB-stirred neutrophils were subdivided into 5 groups by receiving different experimental interventions: (1) bacterial lipopolysaccharide (LPS, 10 ng x ml(-1)), (2) N-formylmethionylphenylalanine (fMLP, 1 micromol x L(-1)), (3) LPS+fMLP, (4) 1-butanol (0.5%)+LPS+fMLP, (5) vehicle. Elastase and myeloperoxidase (MPO) release was measured for the parameters of neutrophil activation, neutrophil PLD activity was determined by quantitation of choline produced from the stable product of phosphatidylcholine catalyzed by PLD.

RESULTS(1) Preoperative neutrophils treated with LPS+fMLP presented significantly higher PLD activity (13.48+/-2.61 nmol choline x h(-1) x mg(-1)) and released more elastase and MPO than cells treated with vehicle (PLD activity 3.70+/-0.49 nmol choline x h(-1) x mg(-1)), P<0.01), LPS (P<0.01) and fMLP respectively. In 1-butanol+LPS+fMLP group, PLD activity of preoperative neutrophils was lower than that in LPS+fMLP group (P<0.01), besides the release of elastase and MPO decreased sharply below both LPS+fMLP and fMLP groups (P<0.01). In LPS group, PLD activity was higher (P<0.01), while elastase and MPO release did not differ from control. fMLP group presented PLD activity, elastase and MPO release higher than control (P<0.01); nevertheless, lower than LPS+fMLP group (P<0.01). (2) CPB-stirred neutrophils presented prominent PLD activity increment, and even the control level was 3.59-fold of the pre-operative control (P<0.01). PLD activity in LPS+fMLP group was higher than that in other groups. Notably, PLD activity was even nonstatistically lower in 1-butanol+LPS+fMLP group than that in LPS or fMLP group. CPB-stirred neutrophils in LPS+fMLP group released more elastase and MPO than control, LPS, and 1-butanol+LPS+fMLP groups did (P<0.01); however, neither of the release was statistically different from that of fMLP group.

CONCLUSIONSCardiopulmonary bypass enables neutrophil priming accompanied with significant increase in PLD activity. Inhibition of neutrophil PLD activation attenuates its priming and may alleviate CPB-induced systemic inflammatory reaction.

Adolescent ; Adult ; Cardiopulmonary Bypass ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Neutrophil Activation ; physiology ; Phospholipase D ; pharmacology ; Systemic Inflammatory Response Syndrome ; etiology ; physiopathology