Expression And Significance Of Icam-1 In Inflammation Of Nervous System

Background and ObjectiveIn the pathophysiology of nervous system diseases such as trauma, infections and degeneration diseases, inflammation is the common character. In the process of these diseases, they all contained the activation of immune cells and the secretion of many kinds of cytokines. These inflammation factors would induce cell immunity, and prevent neurons damage. However, these inflammation mediators would change the balance in internal environment, and destroy the function of normal cells. All the things could promote the process of demyelination disease.Intercellular adhesion molecule-1 (ICAM-1) is a 76–114 kDa cell surface glycoprotein that belongs to the immunoglobulin superfamily of adhesion molecules. It has a cytoplasmic tail, a transmembranous region, and five extracellular domains binding toβ2-integrin counterreceptors lymphocyte function-associated antigen (LFA)-1 and macrophage surface antigen (Mac)-1. The degree of ICAM-1 glycosylation inversely affects its binding to Mac-1 but has little effect on its binding to LFA-1. During inflammation, ICAM-1 can be dramatically up-regulated by bacterial lipopolysaccharid (LPS), phorbol esters, and inflammatory cytokines.The injuries of the peripheral nerve require section of peripheral nerves to gain access to the surgical site, while ICAM-1 is involved in cell recruitment during Wallerian degeneration after peripheral nerve injury. In the central nervous system (CNS), ICAM-1 expression is frequently up-regulated in early phase of inflammatory diseases. ICAM-1 may promote adhesion and migration of leukocytes to inflammatory sites.In the current study, we examined expression and localization changes of ICAM-1 in various kinds of nerve inflammation processes caused by trauma, intraperitoneal and intraspinal injections of LPS to clarity the function of ICAM-1 in the regulation of never inflammation.Methods1. The models were preparated in rats by trauma and LPS intraperitoneal and intraspinal injections.2. The tissue content of ICAM-1 mRNA and protein were assayed by RT-PCR and Western Blot, and the locations of ICAM-1 protein in tissues were detected by double immumofluorescence.3. Cultured Schwann cells were stimulated by LPS. Expression of ICAM-1 was detected by RT-PCR and Western Blot analysis. Immunofluorescent staining was used to observe the effects of LPS on the distribution of ICAM-1. The extracellular signal-regulated kinase (ERK) 1/2 inhibitor, U0126, p38 inhibitor, SB202190, and SAPK/JNK specific inhibitor, SP600125 were used to analysis the signal pathway of LPS-induced ICAM-1 synthesis. Results1. 1) Expression of ICAM-1 in peripheral nervous system including sciatic nerves and the dorsal root ganglia (DRG) following sciatic nerve injury were up-regulated and then decreased to the normal level.2) Double labeling demonstrated the presence of ICAM-1 within both Schwann cells and nerve blood vein endothelia cells in sciatic nerve after injury. In ipsilateral DRG, a few ICAM-1 signals were found in satellite cells, and ICAM-1 staining was mainly distributed in neuron.2. 1) The ICAM-1 mRNA and protein levels in the sciatic nerve at several time points of LPS injection and found that it could be detected at 1 h and especially high at 4 h by using RT-PCR and Western Blot analysis.2) Immunofluorescence double-labeling suggested ICAM-1 expression was in Schwann cells.3) LPS regulated ICAM-1 expression in Schwann cells via the activation of MAPKs, especially p38 and SAPK/JNK pathways, and inhibitors specific to MAPK subgroups could block ICAM-1 expression in SCs.3. 1) ICAM-1, LFA-1 and Mac-1 in the spinal cords of LPS intraspinal injected rats were upregulated as compared to the nomal spinal cords.4. 2) In normal spinal cords, rare ICAM-1 staining was found. In the injected spinal cord ICAM-1 was detected at the side of injection, many ICAM-1 positive cells were found at the injected side, mostly in the grey matter, while the opposite side almost had no expression.5. 3) Double immunofluorescent staining indicated ICAM-1 mostly located in microglia cells, especially those in the anterior horn and dorsal horn.Conclusions1. In normal condition, there is little ICAM-1 expression in sciatic nerves, DRG, spinal cords. Injury and injection LPS by intraperitoneal and intraspinal upregulate ICAM-1 expression in the early phase. These data indicate that ICAM-1 is an inflammatory response molecule participating in the inflammatory process of nervous systerm.2. In PNS, high level of ICAM-1 expression caused by injury and LPS was detected in Schwann cells, suggesting ICAM-1 might involved in the inflammation of Schwann cells.3. Exposure of cell cultures to LPS resulted in obviously changes of ICAM-1 expression. These effects are regulated by p38 and SAPK/JNK signal pathway.4. LPS unregulated ICAM-1 expression in spinal cords and the location of ICAM-1 was found in microglia. These results suggested a possible role of this molecule in microglia mediated immune response and antigen presenting in CNS immune diseases.5. LPS unregulated LFA-1 and Mac-1 expression in spinal cord. This result indicated ICAM-1 might promote microglia activation by interacting with its ligands.