Abstract：OBJECTIVE: To study the expression of stromal cell derived factor-1(SDF-1) in the airway and to investigate the role of SDF-1 receptor antagonist AMD3100 intervention in rats with asthma. METHODS: Thirty Sprague-Dawley rats were randomly divided into three groups: normal control and asthma with and without AMD3100 intervention. The rat model of asthma was prepared by aerosolized ovalbum (OVA) challenge. The AMD3100 intervention group was administered with AMD3100 of 50 μg 30 minutes before challenge every other day, for 10 times. The characteristic airway inflammation and alterations of airway structures were observed by hemetoxylin and eosin staining. The levels of interleukin 4 and interleukin 5 in whole lung homogenates were measured using ELISA. RT-PCR was used to evaluate the expression of SDF-1 mRNA in the lung. RESULTS: The airway wall thickness in the untreated asthma group was greater than that in the control and the AMD3100 intervention groups (P<0.05). The levels of interleukin 4 and interleukin 5 in whole lung homogenates in the AMD3100 intervention group were lower than those in the untreated asthma group (P<0.05). The expression of SDF-1 mRNA in the untreated asthma group was higher than that in the control and the AMD3100 intervention groups (P<0.05). CONCLUSIONS: SDF-1 may be associated with airway inflammation and remodeling in rats with asthma. AMD3100 may reduce the airway inflammation and improve airway remodeling by inhibiting the bioactivity of SDF-1.
ZOU Li-Ping,WANG Li-Xia,ZHANG Yan et al. Expression of SDF-1 in lung tissues and intervention of AMD3100 in asthmatic rats[J]. CJCP, 2011, 13(4): 321-325.
［1］Altenburg JD, Broxmeyer HE, Jin Q, Cooper S, Basu S, Alkhatib G. A naturally occurring splice variant of CXCL12/stromal cell-derived factor 1 is a potent human immunodeficiency virus type 1 inhibitor with weak chemotaxis and cell survival activities［J］. J Virol, 2007, 81(15): 8140-8148.
［2］Negrete-Garcia MC, Velazquez JR, Popoca-Coyotl A, Montes-Vizuet AR, Juárez-Carvajal E, Teran LM. Chemokine (C-X-C motif) ligand 12/stromal cell-derived factor-1 is associated with leukocyte recruitment in asthma［J］. Chest, 2010, 138(1): 100-106.
［7］Hoshino M, Aoike N, Takahashi M, Nakamura Y, Nakagawa T. Increased immunoreactivity of stromal cell-derived factor-1 and angiogenesis in asthma［J］. Eur Respir J, 2003, 21(5):804-809.
［8］Coyle AJ, Wagner K, Bertrand C, Tsuyki S, Bews J, Heusser C. Central role of immunoglobulin (lg)E in the induction of lung eosinophil infiltration and T helper 2 cell cytokine production: inhibition by a non-anaphylatogenic anti-IgE antibody［J］. J Exp Med, 1996, 183(4): 1303-1310.
［9］Gonzalo JA, Lloyd CM, Peled A, Delaney T, Coyle AJ, Gutierrez-Ramos JC. Critical involvement of the chemotactic axis CXCR4/stromal cell-derived factor-1alpha in the inflammatory component of allergic airway disease［J］. J Immunol, 2000, 165(1): 499-508.
［10］Ding Z, Issekutz TB, Downey GP, Waddell TK. L-selectin stimulation enhances functional expression of surface CXCR4 in lymphocytes: implications for cellular activation during adhesion and migration［J］. Blood, 2003, 101(11): 4245-4252.
［11］Zhang S, Qi L, Li M, Zhang D, Xu S ,Wang N, et al. Chemokine CXCL12 and its receptor CXCR4 expression are associated with perineural invasion of prostate cancer［J］. J Exp Clin Cancer Res, 2008, 27: 62.
［12］Carr AN, Howard BW, Yang HT, EbyWilkens E, Loos P, Varbanov A, et al. Efficacy of systemic administration of SDF-1 in a model of vascular insufficiency: support for an endotheliumdependent mechanism［J］. Cardiovasc Res, 2006, 69(4): 925-935.
［13］Su X, Taniuchi N, Jin E, Fujiwara M, Zhang L, Ghazizadeh M, et al. Spatial and phenotypic characterization of vascular remodeling in a mouse model of asthma［J］. Pathobiology, 2008, 75(1): 42-56.
［14］McDonald DM. Angiogenesis and remodeling of airway vasculature in chronic inflammation［J］. Am Respir Crit Care Med, 2001, 164(10 Pt 2): S39-S45.
［15］Lukacs NW, Berlin A, Schols D, Skerlj RT, Bridger GJ. AMD3100, a CxCR4 antagonist, attenuates allergic lung inflammation and airway hyperreactivity［J］. Am Pathol, 2002, 160(4): 1353-1360.
