ABSTRACT
Objective To understand the differences between infiltration of mononuclear-macro-phages and neutrophils during Leptospira interrogans (L.interrogans) infection and the underlying mecha-nisms. Methods Histological changes in mouse lung, liver and kidney tissues were detected using hema-toxylin and eosin (HE) staining following infection of C3H/HeJ mice with L.interrogans serovar Lai strain 56601. Infiltration of peripheral blood-derived CD11b+mononuclear-macrophages and Ly6G+neutrophils in lung,liver and kidney tissues collected form L.interrogans-infected C3H/HeJ mice was detected with immu-nohistochemistry. Levels of mononuclear-macrophage chemokines and neutrophil chemokines in serum sam-ples of L.interrogans-infected mice were detected with chemokine detection microarray. Results Lung,liv-er and kidney tissue samples collected from L. interrogans-infected C3H/HeJ mice presented typical his-topathological changes of leptospirosis, such as inflammatory cell infiltration in these tissues, pulmonary hemorrhage,extensive hepatocyte necrosis and serious nephrohemia. Results of immunohistochemical stai-ning showed that a large number of peripheral blood-derived CD11b+mononuclear-macrophages were presen-ted in lung,liver and kidney tissues of L.interrogans-infected mice, but few neutrophils could be found in these tissues. The mouse chemokine detection microarray confirmed that the levels of mononuclear-macro-phage chemokines (I-309,MCP-1,MCP-5,MIP-1α and RANTES) in serum samples of L.interrogans-in-fected C3H/HeJ mice were significantly increased during infection (P<0.05), but the neutrophil chemokines(KC,LIX and MIP-2) analyzed in this study were not notably increased (P>0.05). Conclu-sion Mononuclear-macrophages rather than neutrophils are the major infiltrating phagocytes during L.inter-rogans infection and play a crucial role in the elimination of Leptospira invasion.
ABSTRACT
Aim To investigate the effect of intrathecal injection of CCR2 antagonist on pain behaviours,spinal astrocytes activation in the spinal cord in a rat model of bone cancer pain. Methods Forty female SD rats weighing 150 ~180 g were randomly divided into five groups ( n=8 each ):(Ⅰ) sham group;(Ⅱ) sham +RS102895 group;(Ⅲ) bone cancer pain group;(Ⅳ) bone cancer pain + DMSO group;(Ⅴ) bone cancer pain+RS102895 group. Rats received i. t. injections of either RS102895 (3 g·L-1 ) 10 μl or 10%DMSO 10 μl at the time of 10-12 days after the operation. Bone cancer was induced by intra-tibial inoculation of 1 × 105 Walker 256 breast cancer cell. Mechanical hind paw withdrawal threshold test was performed one day before and at 3rd,6th,9th, 10th,11th and 12th days after surgery. Immunofluorescence was used to observe the activation of the spinal astrocytes. Results Compared with group Ⅰ, the rats in bone cancer pain group appeared obvious mechanical hyperalgesia (Ⅲ、Ⅳ、Ⅴ) ,the volume,shape and mean optical den-sity ( MOD) of spinal astrocytes could be seen obvious-ly increased,groupⅡhad no obvious statistical signifi-cance (P>0. 05). Compared with group Ⅳ ,i. t. in-jections of RS102895 increased the paw mechanical withdrawal threshold, suppressed the action of astro-cytes,reduced the MOD of spinal astrocytes. Conclu-sion CCR2 might participate in the formation of bone cancer pain via activating spinal astrocytes. CCR2 will be a potential target for the treatment of bone cancer pain.