Search NEL Online

Journal Article 2006; 27(Suppl 2): 160-163 PubMed PMID: 17159805 Citation  Keywords:  Animals, Carbazoles:pharmacology, Cells, Cultured, Immunity, Cellular:drug effects, Immunity, Innate:drug effects, Macrophages:drug effects, Mice, N-Formylmethionine Leucyl-Phenylalanine:pharmacology, Nitric Oxide Synthase Type II:metabolism, Peroxidase:m.   

OBJECTIVES: Neutrophils and macrophages are critical components of our innate host defenses. They are a potential source of nitric oxide (NO) and superoxide, known to play an important role in many physiological processes including defense, immune and inflammatory responses. Myeloperoxidase (MPO), a major NO scavenger and a marker of oxidative stress, as well as increased inducible nitric oxide synthase (iNOS) expression, may affect the NO-superoxide balance, critical for cellular redox balance in the cardiovascular system at physiologic conditions. The effect of carvedilol was studied on stimulated superoxide generation, MPO release and iNOS expression in phagocytes by using receptor operating stimuli [N-formyl-Met-Leu-Phe (FMLP), lipopolysaccharide (LPS) and specific inhibitors (wortmannin, propranolol).

METHODS: Superoxide generation was measured as superoxide dismutase inhibitable reduction of cytochrome c (550 nm), MPO activity as the oxidation of o-dianisidine in the presence of hydrogen peroxide in a spectrophotometer Hewlet Packard 8452 A (463 nm). Expression of iNOS (Western-blot analysis) in RAW 264.7 cell line (murine macrophages) was stimulated by lipopolysaccharide (LPS).

RESULTS: Carvedilol dose-dependently decreased superoxide generation and MPO release from intact neutrophils stimulated by FMLP. In the highest concentration tested, carvedilol pronounced the effect of wortmannin [inhibitor of phospholipase D (PLD) regulatory pathway] and significantly decreased LPS stimulated iNOS expression in RAW 264.7 cell line.

CONCLUSION: The conceivable cumulative non-specific membrane effect of carvedilol and its effect on PLD signalling pathway contribute to the decrease of both superoxide generation and MPO release, thus supporting the restoration of NO-superoxide balance....

Read abstract

Journal Article 2005; 26(1): 55-60 PubMed PMID: 15726021 Citation  Keywords:  Animals, Cells, Cultured, Cricetinae, Female, Immunity:physiology, Inflammation:immunology, Leukocytes:immunology, Macrophages:immunology, Male, Peritonitis:chemically induced, Phagocytosis:physiology, Phodopus, Photoperiod, Phytohemagglutinins:pharmacolo.   

OBJECTIVES: Siberian hamsters are photoperiodic animals exhibiting seasonality of reproduction and other physiological functions. Thus, the influence of photoperiod on the in vitro activity of selected immune cells from male and female hamsters challenged with peritoneal inflammation was examined.

METHODS: Animals were housed for 8-10 weeks in LD (L:D=18:6) or SD (L:D=6:18). Peritoneal leukocytes (PTLs) and splenocytes were isolated form male and female and testicular macrophages (TMs) from male hamsters, intact or challenged with zymosan-induced peritonitis. PTL and TM activity was assessed by the level of reactive oxygen species (ROS) measured with the use of flow cytometry and splenocyte activity -- by the spontaneous and mitogen-stimulated proliferation measured with the use of 3H-tymidine incorporation test.

RESULTS: Results obtained indicate that the immune system of Siberian hamsters is highly sexually dimorphic. Experimentally evoked peritonitis developed differently in males and females: only in LD male hamsters an increase in PTL activity was observed after zymosan treatment. Also, in LD males, PTL activity was higher in LD than in SD. Developing peritonitis exerted in these animals a stimulatory effect on splenocyte proliferation but had no influence on cells residing in the immune privileged testes. Splenocyte proliferation, both spontaneous and PHA-stimulated, depended on the photoperiod studied: in LD it was significantly higher than in SD in animals of both sexes.

CONCLUSIONS: Innate immunity of Siberian hamsters studied on the peritoneal inflammation model, seems to be gender- and photoperiod dependent. Moreover, local inflammation may affect other lymphoid organs but does not influence immune-privileged sites....

Read abstract  Full text PDF

Journal Article 2001; 22(1): 19-26 PubMed PMID: 11335875 Citation  Keywords:  Animals, Apoptosis, Basement Membrane:ultrastructure, Cell Movement, Cerebral Cortex:injuries, Cytoplasm:ultrastructure, Endothelium, Vascular:ultrastructure, Intercellular Junctions:ultrastructure, Macrophages:ultrastructure, Necrosis, Phagocytosis, Rats.   

OBJECTIVES: The effect of the traumatic injury of the cerebral cortex on the ultrastructure of the cerebrovascular junction was studied in rats. The aim of the present study is to describe the ultrastructural alterations in the cerebrovascular junction in rat cerebral cortex after traumatic injury. We were particularly interested in the alterations in endothelium, pericytes and the differentiated population of cerebral macrophages.

MATERIAL AND METHODS: The observations were conducted four days (group I-five animals) and seven days (group II-five animals) after induction of cortical trauma. Traumatic injury was induced in the fronto-temporal region of cerebral cortex in general anesthesia with 20 mg/kg ketamine hydrochloride.

RESULTS: In the first group we found the features of damage of the blood-brain barrier and migration of the morphological blood components to the perivascular space. The trauma caused necrosis and apoptosis within brain tissue. An important observation was the presence of numerous brain macrophages that participated in phagocytosis of damaged cellular elements. Additionally, we found an increase in the connective tissue ground substance around brain capillaries. In the second experimental group we noted an increased number of pericytes (1-3) near capillary walls. In some instances, the basement membrane surrounding the pericytes was interrupted and these cells were also located beyond the rim of the vessel wall. Some pericytes showed numerous phagolysosomes indicating that these cells belonged to perivascular macrophages. Moreover, we observed a population of phagocytes residing in close contact with neurons. These cells were different from the typical perivascular macrophages.

CONCLUSIONS: These observations indicate that the traumatic injury of the brain results in mobilization of a heterogeneous population of brain macrophages. This study indicates that different subpopulations of macrophages emerge in the region of traumatic brain damage, and that the morphology and dynamics of these phagocytes changes and depends on the time elapsed after the initial traumatic incident....

Read abstract  Full text PDF