五味子酚对大鼠嗜中性白细胞功能与形态的作用(英文)

目的:探讨五味子酚(Sal)对大鼠嗜中性白细胞(Neu)功能的调节作用.结果:Sal 1,10,100μmol·L~(-1)剂量依赖性抑制Neu功能,Sal 100μmol·L~(-1)使Neu表面伪足和皱褶消失,并可降低细胞内钙离子浓度、升高细胞内cAMP水平.结论:Sal可通过影响细胞内钙离子浓度、cAMP水平及细胞表面形态抑制Neu的功能.     

ISCHAEMIA-REPERFUSION INJURY TO THE INTESTINE

Ischaemia-reperfusion injury (IRI) is of obvious relevance in situations where there is an interruption of blood supply to the gut, as in vascular surgery, or in the construction of free intestinal grafts. It is now appreciated that IRI also underlies the gut dysfunction that occurs in early shock, sepsis, and trauma. The events that occur during IRI are complex. However, recent advances in cellular biology have started to unravel these underlying processes. The aim of this review is to provide an outline of current knowledge on the mechanisms and consequences of IRI. Initially, IRI appears to be mediated by reactive oxygen metabolites and, at a later stage, by the priming and activation of polymorphonuclear neutrophils (PMN). Ischaemia-reperfusion injury can diminish the barrier function of the gut, and can promote an increase in the leakage of molecules (intestinal permeability) or the passage of microbes across the wall of the bowel (bacterial trans-location). Ischaemia-reperfusion injury to the gut can result in the generation of molecules that may also harm distant tissues.     

Intracellular bioactivity of macrolides

A brief overview is provided of the bioactivity of macrolides against a range of bacterial species. Topics considered include the cellular pharmacokinetics of uptake and efflux of these drugs and the importance of intra- or extracellular and cytoplasmic or granular location on their activity. Emphasis is placed on the importance of synergy between macrolides and host defenses, with drug accumulation producing modification of cellular function, such as enhancement of phagocytosis, and exocytosis of polymorphonuclear neutrophils. Such interaction may explain the activity of such agents against organisms which normally inhibit fusion of phagolysosomes.     

Antibody-dependent neutrophil-mediated parasite killing in non-lethal rodent malaria

The effects of administrating recombinant human granulocyte colony-stimulating factor (rhG-CSF) and passively transferring immune serum on infection with an attenuated variant of Plasmodium berghei XAT (Pb XAT), in severe combined immunodeficiency (SCID) mice were examined. In immune competent (C.B-17) mice, the attenuated parasite infection was inevitably self-resolving and degenerating forms inside erythrocytes appeared, coinciding with the drop in parasitaemia, whereas SCID mice were unable to control parasite growth and all the mice died. Continuous administration with rhG-CSF caused neutrophilic granulocytosis in both SCID and C.B-17 mice. The effect of rhG-CSF on the infection in C.B-17 mice was to suppress the course of the parasitaemia at an early phase whereas it had no effect in SCID mice. When immune serum was transferred on the day of infection, the prepatent period was prolonged two days in both SCID and C.B-17 mice. When administration with rhG-CSF was combined with transfer of immune serum, SCID mice showed four days delay in patency and degenerating parasites were seen during the course of parasitaemia, although the infection was ultimately fatal. C.B-17 mice similarly treated showed a seven day delay in the onset of the patent parasitaemia which was of a lesser magnitude and shorter in duration compared with control mice. On the other hand, when C.B-17 mice were splenectomized three weeks before infection and then treated with rhG-CSF and immune serum, no degenerating parasites were seen during the infection and all mice died with high parasitaemias. These results show that antibody-dependent neutrophil-mediated parasite killing may occur in the spleen of mice infected with P. berghei XAT.     

Effects of obstructive jaundice on neutrophil production and acquisition of chemotactic activity in the bone marrow

Background and Aims:  Increased numbers and enhanced functions of peripheral neutrophils have been observed in obstructive jaundice. However, the effects of obstructive jaundice on the bone marrow, that is neutrophil production and acquisition of neutrophil chemotactic activity, have been poorly understood. In the present study, differentials of bone marrow cells and chemotactic activity of bone marrow neutrophils were evaluated in bile duct-obstructed rats.
Methods:  Male Wistar rats underwent either bile duct obstruction for 10 days or bile duct obstruction for 4 days followed by 6 days' internal biliary drainage. Differentials of peripheral blood and bone marrow cells were sequentially determined. Chemotactic activity of peripheral and bone marrow neutrophils was evaluated with a modified Boyden method using interleukin-8 (recombinant rat Gro-β) as a chemoattractant.
Results:  Numbers of peripheral neutrophils significantly increased after bile duct obstruction. Significant increases in the myeloid/erythroid (M/E) ratio of bone marrow cells were observed after bile duct obstruction. The neutrophil proliferative pool (promyelocytes and myelocytes) increased initially, followed by an increased neutrophil storage pool (metamyelocytes, bands, and segmented neutrophils). The M/E ratio as well as the neutrophil proliferative and storage pools normalized after internal biliary drainage. Chemotactic activity was enhanced in both peripheral and bone marrow neutrophils after bile duct obstruction, and enhanced chemotaxis was alleviated with internal biliary drainage.
Conclusion:  The present results strongly suggest the principal role of the bone marrow in increasing the number of neutrophils and their chemotactic activity during obstructive jaundice.     

Association between inflammation and epithelial damage-restitution processes in allergic airways in vivo

Background Associations between allergen challenge-induced sites of epithelial damage and the distribution of leucocytes and extravasated plasma remain unexplored. Objective To study neutrophils, eosinophils, and fibrinogen at allergen challenge-induced patchy epithelial damage-restitution sites in guinea-pig trachea. Methods After local challenge tracheal tissue (cryo sections and whole-mounts) and lumen (selective tracheal lavage) were examined at 1, 5, and 24 h. Eosinophils, neutrophils and fibrinogen were identified by histochemistry. Results Neutrophils increased markedly in tracheal lavage fluids and in tissue and were strongly associated with the challenge-induced epithelial craters of damage-restitution. At 1 and 24 h eosinophils were increased in the tracheal lumen whereas the surrounding tissue displayed a reversed pattern. Gels rich in fibrinogen, neutrophils, and eosinophils were present in epithelial crater areas, protruding into the lumen. Clusters of free eosinophil granules, Cfegs, released through lysis of eosinophils, and neutrophils with long cytoplasmatic protrusions abounded in these crater areas. Conclusions The present findings provide important new insights into allergic airways where sites of epithelial damage-restitution processes emerge as the major loci for eosinophil, neutrophil, and plasma protein activities, the latter likely causing leukocyte adhesion and activation in vivo. The disttibution of eosinophils in this study suggests roles of these cells both in airway mucosa and in regional lymph nodes. Based on the present study we also propose that lysis of eosinophils and Cfegs generation are a major paradigm for activation of these cells in vivo.     

Neutrophil superoxide release and interleukin 8 in acute myocardial infarction: distinction between complicated and uncomplicated states

Superoxide release in neutrophils and sera levels of interleukin 8 (IL-8) were determined in 15 patients with complicated acute myocardial infarction (MI) and 15 patients with uncomplicated MI. All patients showed increased superoxide release in unstimulated and stimulated neutrophils compared with healthy control subjects, indicating priming of these cells. Superoxide release of unstimulated or stimulated neutrophils was found to be significantly higher in patients with complicated MI than in patients with uncomplicated MI. Thrombolytic therapy did not affect the rates of superoxide release. The neutrophil chemoattractant/activator IL-8 was detected in the sera of all patients, with significantly higher levels in those with complicated MI. The highest levels of IL-8 were detected at admission to the Coronary Care Unit and significantly decreased thereafter, suggesting its contribution to neutrophil-mediated tissue injury. The high levels of IL-8 may be one of the major contributors to the priming of neutrophils in these patients.     

Identification of neutrophil chemotactie factors in bronchoalveolar lavage fluid of asthmatic patients

Background Although neutrophils have been implicated in bronchial asthma, the mechanism(s) which bring these cells into the airways is poorly understood. Objective To investigate the presence and identity of neutrophil chemotactic factors in bronchoalveolar lavage (BAL) fluid from atopic asthmatic subjects. Method BAL fluid was obtained from 13 subjects (seven asthmatics and six normals). aged 19 to 60 yr, at bronchoscopy. Separation of neutrophil chemotactic activity (NCA) was achieved by FPLC cation exchange chromatography. Fractions were collected and assayed for chemotaxis multiwell micro-chemotaxes chambers using polycarbonate filters, for the complement peptide C5a/C5a des Arg by radioimmunoassay (RIA) and for interleukin-8 (IL-8) by ELISA. Results NCA was found in FPLC fractions of BAL samples in four out of seven asthmatics and each of these subjects had at least three similar peaks of NCA. The major peak of NCA was found to contain immunoreactive C5a/C5a des Arg and chemotaxis. In response to this NCA could be blocked by desensitization of the neutrophils with recombinant C5a. Purified serum derived C5a/C5a des Arg was found to have altered chromatographic properties when added to BAL fluid; this suggested that BAL fluid contained proteins which interacted with the C5a/C5a des Arg. Immunoreactive IL-8 (iIL-8) was also detected but its concentration or chemical form was insufficient to induce neutropbil chemotaxis. Conclusion This study demonstrates that bronchial asthmatic lavage fluid contains C5a/C5a des/Arg and iL-8, together with other as yet unidentified factors which may contribute to neutropbil recruitment in this disease.     

LTB4 is present in exudative pleural effusions and contributes actively to neutrophil recruitment in the inflamed pleural space

The pleural space is a virtual compartment between the lung and chest wall that becomes filled with fluid and inflammatory cells during a variety of respiratory diseases. Here, we study the potential role of the eicosanoid metabolite leukotriene B4 (LTB4) in disparate diseases leading to acute (pneumonia) or chronic (tuberculosis, cancer) inflammation of the pleural space. LTB4 concentrations were significantly higher in pleural fluid due to pneumonia, tuberculosis and cancer with respect to congestive heart failure and correlated with neutrophil elastase, which is used as an indication of state of activation of neutrophils in the pleural space. Moreover, pleural LTB4 was biologically active, as an anti-LTB4 antibody partially neutralized the chemotactic activity of parapneumonic, tuberculous and cancer effusions. Macrophages, neutrophils, lymphocytes, mesothelial cells and cancer cells all expressed mRNA for 5-lipoxygenase, the enzyme that initiates leukotriene synthesis leading to the production of LTB4, in exudative pleural effusions. Upon stimulation in transudative pleural effusions, pleural macrophages produced, in a time-dependent fashion, a significantly higher concentration of LTB4 than mesothelial cells. These studies demonstrate that different cell types are capable of producing LTB4 in the inflamed pleural space and that this mediator may play a crucial role in the recruitment of neutrophils into the pleural space.