OBJECTIVETo compare the differences of neutrophils chemotaxis ability in peritoneal cavity between normal rats and schizopherenic rats with cell dynamic visualization system.METHODSIn the study,18 healthy Kunming rats were randomly divided into 3 groups which were control group (n=6), 0.3 mg/kg MK-801 treatment group (n=6), 0.6 mg/kg dizocilpine maleate (MK-801) treatment group(n=6), extracted neutrophils separately, and observed the morphology and counted under a microscope. Each group of cells was divided into two parts for chemotactic experiment, called chemokine agent treatment group and no chemokine agent treatment group respectively, indicating control 1, 0.3 mg/kg MK-801 treatment 1,0.6 mg/kg MK-801 treatment 1 and control 2, 0.3 mg/kg MK-801 treatment 2,0.6 mg/kg MK-801 treatment 2. The dynamic migration of cells was recorded using the NIS-Elements software, and TAXIScan Analyzer 2 software was used to select 30 cells (n=30) in each group of cells and analyze cells migration trajectory, speed and distance, and use pair test and One-Way analysis of variance for statistical analysis.RESULTSThe number of neutrophils in control group, 0.3 mg/kg MK-801 treatment group and 0.6 mg/kg MK-801 treatment group were(1.00±0.03)×10⁴/mL,(0.05±0.02)×10⁴/mL,(0.32±0.01)×10⁴/mL respectively, the differences of results were statistically significant(P<0.05).Under the effect of chemotactic agent,the directional migration capability of neutrophils in control group 1, 0.3 mg/kg MK-801 treatment group 1 and 0.6 mg/kg MK-801 treatment group 1 were(0.85±0.11) radian,(1.00±0.11) radian,(0.96±0.10) radian respectively (P<0.05); the migration velocities of neutrophils were (0.09±0.02) μm/s,(0.12±0.01) μm/s,(0.14±0.01) μm/s respectively (P<0.05);the migration distances of neutrophils were (94.26±0.02) μm,(134.61±0.01) μm,(156.19±0.01) μm respectively(P<0.05).CONCLUSIONCompared with neutrophils in peritoneal cavity of control group, the neutrophils in peritoneal cavity of schizophrenic rats have stronger chemotactic movement ability.

2008-09-01·European Journal of Pharmacology3区 · 医学

Elevated level of the proinflammatory chemokine, RANTES/CCL5, in the periaqueductal grey causes hyperalgesia in rats

3区 · 医学

Article

作者: Khalid Benamar ; Martin W. Adler ; Ellen B. Geller

The present data provide the first in vivo evidence that the proinflammatory chemokine, Regulated on Activation Normal T cell Expressed and Secreted (RANTES/CCL5) microinjected directly into the periaqueductal grey in rats, a brain region critical to the processing of pain signals, and a primary site of action of many analgesic compounds, induced hyperalgesia. Pretreatment with antibodies against RANTES/CCL5 prevented the hyperalgesic response, indicating that RANTES/CCL5 is able to interfere with the control of hyperalgesia at the level of the periaqueductal grey and suggesting that chemokine blockers could have analgesic properties.

2006-08-15·Journal of Virology2区 · 医学

Role of CCL5 (RANTES) in Viral Lung Disease

2区 · 医学

Article

作者: Wells, Timothy N. ; Walzl, Gerhard ; Pennycook, Alasdair M. J. ; Dodd, Jonathan S. ; Hussell, Tracy ; Openshaw, Peter J. M. ; Tregoning, John S. ; Culley, Fiona J.

ABSTRACTCCL5/RANTES is a key proinflammatory chemokine produced by virus-infected epithelial cells and present in respiratory secretions of asthmatics. To examine the role of CCL5 in viral lung disease, we measured its production during primary respiratory syncytial virus (RSV) infection and during secondary infection after sensitizing vaccination that induces Th2-mediated eosinophilia. A first peak of CCL5 mRNA and protein production was seen at 18 to 24 h of RSV infection, before significant lymphocyte recruitment occurred. Treatment in vivo with Met-RANTES (a competitive chemokine receptor blocker) throughout primary infection decreased CD4+and CD8+cell recruitment and increased viral replication. In RSV-infected, sensitized mice with eosinophilic disease, CCL5 production was further augmented; Met-RANTES treatment again reduced inflammatory cell recruitment and local cytokine production. A second wave of CCL5 production occurred on day 7, attributable to newly recruited T cells. Paradoxically, mice treated with Met-RANTES during primary infection demonstrated increased cellular infiltration during reinfection. We therefore show that RSV induces CCL5 production in the lung and this causes the recruitment of RSV-specific cells, including those making additional CCL5. If this action is blocked with Met-RANTES, inflammation decreases and viral clearance is delayed. However, the exact effects of chemokine modulation depend critically on time of administration, a factor that may potentially complicate the use of chemokine blockers in inflammatory diseases.

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