过敏毒素C3a及白细胞介素-32在慢性阻塞性肺疾病气道炎症中的作用
摘要
目的探讨过敏毒素C3a及白细胞介素-32(IL-32)在慢性阻塞性肺疾病(COPD)气道炎症中的作用。方法纳入COPD稳定期患者30例,COPD急性加重期(AECOPD)患者30例,健康对照者10例。收集受试者痰液及静脉血,应用实时荧光定量逆转录-聚合酶链式反应(RT-PCR)检测痰细胞裂解液及静脉血细胞裂解液中C3和IL-32 mRNA的表达,应用酶联免疫吸附试验(ELISA)检测痰上清液及静脉血清中C3a和IL-32蛋白的表达,分析C3a与IL-32、IL-32与COPD患者肺功能损伤的相关性。结果 AECOPD患者痰细胞裂解液及静脉血细胞裂解液中C3和IL-32 mRNA水平显著升高,痰上清液及静脉血清中C3a和IL-32蛋白水平显著升高。AECOPD患者静脉血清中IL-32蛋白浓度与C3a蛋白浓度呈显著正相关,IL-32蛋白浓度与1 s用力呼气容积(FEV1)占预计值百分比(FEV1%预计值)及FEV1/用力肺活量(FVC)呈显著负相关。结论 C3a通过诱导IL-32促进COPD气道炎症,加重肺功能损害,这将为COPD的诊断和治疗提供有效的靶位。
引文
[1]Vestbo J,Hurd SS,AgustíAG,et al.Global strategy for the diagnosis,management,and prevention of chronic obstructive pulmonary disease:GOLD executive summary[J].Am J Respir Crit Care Med,2013,187(4):347-365.
[2]Afonso AS,Verhamme KM,Sturkenboom MC,et al.COPD in the general population:prevalence,incidence and survival[J].Respir Med,2011,105(12):1872-1884.
[3]Marc MM,Korosec P,Kosnik M,et al.Complement factors c3a,c4a,and c5a in chronic obstructive pulmonary disease and asthma[J].Am J Respir Cell Mol Biol,2004,31(2):216-219.
[4]Abelseth TK,Stensvag K,Espelid S,et al.The spotted wolffish(Anarhichas minor Olafsen)complement component C3:isolation,characterisation and tissue distribution[J].Fish Shellfish Immunol,2003,15(1):13-27.
[5]Kim SH,Han SY,Azam TA,et al.Interleukin-32:a cytokine and inducer of TNFalpha[J].Immunity,2005,22(1):131-142.
[6]Kobayashi H,Yazlovitskaya EM,Lin PC.Interleukin-32 positively regulates radiation-induced vascular inflammation[J].Int J Radiat Oncol Biol Phys,2009,74(5):1573-1579.
[7]Oh JH,Cho MC,Kim JH,et al.IL-32γinhibits cancer cell growth through inactivation of NF-κB and STAT3 signals[J].Oncogene,2011,30(30):3345-3359.
[8]Barnes PJ.Histone deacetylase-2 and airway disease[J].Ther Adv Respir Dis,2009,3(5):235-243.
[9]Abbas AK,Lichtman AH,David L.Cellular and Mocecular Immunology[M].4th ed.Philadelphia:W.B.Saunders Co.2000:290-293.
[10]Fukuoka Y,Xia HZ,Dellinger AL,et al.Generation of anaphylatoxins by human beta-tryptase from C3,C4,and C5[J].J Immunol,2008,180(9):6307-6316.
[11]Huber-Lang M,Sarma JV,Zetoune FS,et al.Generation of C5a in the absence of C3:a new complement activation pathway[J].Nat Med,2006,12(6):682-687.
[12]Zhou JL,Jang YP,Kim SR,et al.Complement activation by photooxidation products of A2E,a lipofuscin constituent of the retinal pigment epithelium[J].Proc Natl Acad Sci U S A,2006,103(44):16182-16187.
[13]Zhou W.The new face of anaphylatoxins in immune regulation[J].Immunobiology,2012,217(2):225-234.
[14]Goda C,Kanaji T,Kanaji S,et al.Involvement of IL-32 in activation-induced cell death in T cells[J].Int Immunol,2006,18(2):233-240.
[15]Choi JD,Bae SY,Hong JW,et al.Identification of the most active interleukin-32 isoform[J].Immunology,2009,126(4):535-542.
[16]Khawar B,Abbasi MH,Sheikh N.A panoramic spectrum of complex interplay between the immune system and IL-32 during pathogenesis of various systemic infections and inflammation[J].Eur J Med Res,2015,20(1):7.
[17]Park MH,Song MJ,Cho MC,et al.Interleukin-32 enhances cytotoxic effect of natural killer cells to cancer cells via activation of death receptor 3[J].Immunology,2012,135(1):63-72.
[18]Yun HM,Oh JH,Shim JH,et al.Antitumor activity of IL-32βthrough the activation of lymphocytes,and the inactivation of NF-κB and STAT3 signals[J].Cell Death Dis,2013,4:e640.
[19]Zeng Q,Li S,Zhou Y,et al.Interleukin-32 contributes to invasion and metastasis of primary lung adenocarcinoma via NF-kappa B induced matrix metalloproteinases 2 and 9 expression[J].Cytokine,2014,65(1):24-32.
[20]Meyer N,Christoph J,Makrinioti H,et al.Inhibition of angiogenesis by IL-32:Possible role in asthma[J].J Allergy Clin Immunol,2012,129(4):964-973.
[21]Rong Y,Xiang XD,Li YM,et al.IL-32 was involved in cigarette smoke-induced pulmonary inflammation in COPD[J].Clin Respir J,2015,9(4):430-435.
[2]Afonso AS,Verhamme KM,Sturkenboom MC,et al.COPD in the general population:prevalence,incidence and survival[J].Respir Med,2011,105(12):1872-1884.
[3]Marc MM,Korosec P,Kosnik M,et al.Complement factors c3a,c4a,and c5a in chronic obstructive pulmonary disease and asthma[J].Am J Respir Cell Mol Biol,2004,31(2):216-219.
[4]Abelseth TK,Stensvag K,Espelid S,et al.The spotted wolffish(Anarhichas minor Olafsen)complement component C3:isolation,characterisation and tissue distribution[J].Fish Shellfish Immunol,2003,15(1):13-27.
[5]Kim SH,Han SY,Azam TA,et al.Interleukin-32:a cytokine and inducer of TNFalpha[J].Immunity,2005,22(1):131-142.
[6]Kobayashi H,Yazlovitskaya EM,Lin PC.Interleukin-32 positively regulates radiation-induced vascular inflammation[J].Int J Radiat Oncol Biol Phys,2009,74(5):1573-1579.
[7]Oh JH,Cho MC,Kim JH,et al.IL-32γinhibits cancer cell growth through inactivation of NF-κB and STAT3 signals[J].Oncogene,2011,30(30):3345-3359.
[8]Barnes PJ.Histone deacetylase-2 and airway disease[J].Ther Adv Respir Dis,2009,3(5):235-243.
[9]Abbas AK,Lichtman AH,David L.Cellular and Mocecular Immunology[M].4th ed.Philadelphia:W.B.Saunders Co.2000:290-293.
[10]Fukuoka Y,Xia HZ,Dellinger AL,et al.Generation of anaphylatoxins by human beta-tryptase from C3,C4,and C5[J].J Immunol,2008,180(9):6307-6316.
[11]Huber-Lang M,Sarma JV,Zetoune FS,et al.Generation of C5a in the absence of C3:a new complement activation pathway[J].Nat Med,2006,12(6):682-687.
[12]Zhou JL,Jang YP,Kim SR,et al.Complement activation by photooxidation products of A2E,a lipofuscin constituent of the retinal pigment epithelium[J].Proc Natl Acad Sci U S A,2006,103(44):16182-16187.
[13]Zhou W.The new face of anaphylatoxins in immune regulation[J].Immunobiology,2012,217(2):225-234.
[14]Goda C,Kanaji T,Kanaji S,et al.Involvement of IL-32 in activation-induced cell death in T cells[J].Int Immunol,2006,18(2):233-240.
[15]Choi JD,Bae SY,Hong JW,et al.Identification of the most active interleukin-32 isoform[J].Immunology,2009,126(4):535-542.
[16]Khawar B,Abbasi MH,Sheikh N.A panoramic spectrum of complex interplay between the immune system and IL-32 during pathogenesis of various systemic infections and inflammation[J].Eur J Med Res,2015,20(1):7.
[17]Park MH,Song MJ,Cho MC,et al.Interleukin-32 enhances cytotoxic effect of natural killer cells to cancer cells via activation of death receptor 3[J].Immunology,2012,135(1):63-72.
[18]Yun HM,Oh JH,Shim JH,et al.Antitumor activity of IL-32βthrough the activation of lymphocytes,and the inactivation of NF-κB and STAT3 signals[J].Cell Death Dis,2013,4:e640.
[19]Zeng Q,Li S,Zhou Y,et al.Interleukin-32 contributes to invasion and metastasis of primary lung adenocarcinoma via NF-kappa B induced matrix metalloproteinases 2 and 9 expression[J].Cytokine,2014,65(1):24-32.
[20]Meyer N,Christoph J,Makrinioti H,et al.Inhibition of angiogenesis by IL-32:Possible role in asthma[J].J Allergy Clin Immunol,2012,129(4):964-973.
[21]Rong Y,Xiang XD,Li YM,et al.IL-32 was involved in cigarette smoke-induced pulmonary inflammation in COPD[J].Clin Respir J,2015,9(4):430-435.