生长抑素诱导猕猴外周血中性粒细胞凋亡
许兰涛, 唐承薇, 四川大学华西医院消化内科 四川省成都市 610041
许兰涛,男, 1964-07-03生, 副主任医师, 副教授, 博士, 主要从事消化内科的研究.
国家自然科学基金资助项目, No. 30170875
项目负责人: 唐承薇, 610041, 四川省成都市, 四川大学华西医院消化内科. sccdlx@sohu.com
电话: 028-85445341
收稿日期: 2004-12-22 接受日期: 2005-01-20
Effect of somstostatin on apoptosis of polymorphonuclear neutrophils of rhesus monkey
Lan-Tao Xu, Cheng-Wei Tang
Lan-Tao Xu, Cheng-Wei Tang, Department of Digestology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Supported by National Science Foundation of China, No.30170875
Correspondence to: Cheng-Wei Tang, Department of Digestology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China. sccdlx@sohu.com
Received: 2004-12-22 Accepted: 2005-01-20
Abstract
AIM: To study the effect of somstostatin on the apoptosis of polymorphonuclear neutrophils (PMNs) in rhesus monkey.
METHODS: PMNs were isolated from whole blood of normal rhesus monkey using one-step discontinuous Percoll gradient centrifugation technique. PMNs were cultured with 5´10-5mol/L somstostatin. Cell morphology was examined by light and electronic microscopy. Apoptosis was detected by flow cytometry and DNA agarose electrophoresis.
RESULTS: Somstostatin at 5´10-5mol/L induced significant apoptosis in PMNs. The cells manifested typical apoptotic morphology: cell membrane blebbing, chromatin condensation, nucleic fragmentation and apoptotic body formation. Agarose electrophoresis revealed specific DNA ladder. Flow cytometry analysis showed that the ratio of PMNs undergoing apoptosis was remarkably increased from 22.1% to 50.5% following somstostatin treatment (P<0.01).
CONCLUSION: Somstostatin induces apoptosis of PMNs in rhesus monkey. It may be a new target for the treatment of multiple organ dysfunction syndrome (MODS).
Key Words: PMN; Apoptosis; Somatostatin; Rhesus monkey; MODS
Xu LT, Tang CW. Effect of somstostatin on apoptosis of polymorphonuclear neutrophils of rhesus monkey. Shijie Huaren Xiaohua Zazhi 2005;13(5):617-620
摘要
目的: 观察生长抑素对猕猴外周血中性粒细胞的作用.
方法: 用生长抑素与猕猴外周血中性粒细胞共同孵育一定时间后,采用流式细胞仪、DNA电泳、电镜观察猕猴外周血中性粒细胞的形态变化,细胞DNA含量分布变化.
结果: 生长抑素能诱导猕猴外周血中性粒细胞凋亡,在形态学上表现为细胞膜起泡、染色质固缩、核碎裂、凋亡小体形成;电泳呈凋亡特征性Ladder带;流式细胞仪分析显示,PMN凋亡比例增高(22.1%vs50.5%. P<0.01).
结论: 生长抑素能诱导猕猴外周血中性粒细胞凋亡.
关键词: 猕猴; 生长抑素; 中性粒细胞; 凋亡; 多器官功能衰竭
许兰涛, 唐承薇. 生长抑素诱导猕猴外周血中性粒细胞凋亡. 世界华人消化杂志 2005;13(5):617-620
:无凋亡图; B:凋亡.
表1 不同浓度生长抑素对PMN凋亡率的影响
P<0.01vs对照组.
2.3 DNA电泳结果 将5´108/L PMN细胞与5´10-5 mol/L生长抑素作用30 min,DNA电泳呈明显凋亡带,对照组则无凋亡带(图2).
图2 (PDF) DNA电泳Ladder带.
2.4 电镜观察 将5´108/L PMN细胞与5´10-5 mol/L生长抑素作用30 min,电镜下可见染色质固缩,聚集于核膜下成块状,胞核固缩,染色质凝集,细胞质浓缩,部分细胞碎裂成片,形成质膜包被的大小不等的凋亡小体(图3).
图3 中性粒细包超微结构TEM×8000.A: 正常; B:凋亡; C:凋亡小体.
3 讨论由于分子生物学发展,尤其是抗炎症递质治疗在临床应用中并不理想后,国内外学者转向炎症递质调控凋亡的研究,就凋亡和MODS发生机制作了新的探讨.Haslett[22-26]提出炎症反应的失调与中性粒细胞凋亡比率有关.Keel[27-30]在MODS研究中发现外周血中中性粒细胞(PMN)凋亡延迟,并且血中有抗凋亡因子存在.认为凋亡延迟引起PMN寿命延长可能与MODS发生有关.Goris[31]提出经过特异性细胞因子触发凋亡可以解释进行性过度炎症反应可以发展到MODS的最后假说.
目前已经明确MODS是过度炎症反应的结果,在创伤后有MODS高风险的患者中,PMN凋亡延迟,血浆中的递质使PMN凋亡延迟,并且PMN的作用引发过度炎症反应及器官损伤,创伤后PMN的凋亡在MODS的发生发展中可能具有重要作用.凋亡区别于坏死的重要之处是凋亡的细胞能被巨噬细胞或周围组织细胞平稳识别、清除而不引发炎症反应,因此有研究认为通过凋亡方式清除炎症部位的PMN是限制组织损伤,促进炎症吸收的重要机制.识别清除凋亡PMN的能力降低,大量凋亡的PMN不能被及时有效地处理而裂解坏死,炎症不易控制,因此这种损伤很容易导致MODS.本实验研究表明:生长抑素能诱导中性粒细胞凋亡,可以减少氧自由基、蛋白酶和炎性递质的释放,有利于巨噬细胞的吞噬,必将为治疗MODS开辟新的领域.
4 参考文献1 Diamond RD, Clark RA, Haudenschild CC. Damage to Candida albicans hyphae and pseudohyphae by the
myeloperoxidase system and oxidative products of neutrophil metabolism in vitro. J Clin Invest 1980;66:908-917
2 Sweeney JF, Nguyen PK, Omann G, Hinshaw DB. Granulocyte-macrophage colony-stimulating factor rescues human
polymorphonuclear leukocytes from ultraviolet irradiation-accelerated apoptosis. J Surg Res 1999;81:108-112
3 Suzuki K, Hasegawa T, Sakamato C, Zhou YM, Hato F, Hino M, Tatsumi N, Kitagawa S. Cleavage of mitogen-activated
protein kinases in human neutrophils undergoing-apoptosis: Role in decreased responsiveness to inflammatory cytokines.
J Immunol 2001;166:1185-1192
4 Sweeney JF, Nguyen PK, Hinshaw DB. Caspase-3 inhibition partially protects oxidant production in apoptotic human
neutrophils. J Surg Res 2001;98:66-70
5 Sun XM, MacFarlane M, Zhuang J, Wolf BB, Green DR, Cohen GM. Distinct caspase cascades are initiated in receptor
mediated and chemical induced apoptosis. J Biol Chem 1999;274:5053-5060
6 Kobayashi SD, Voyich JM, DeLeo FR. Regulation of the neutrophil-mediated inflammatory response to infection.
Microbes Infect 2003;5:1337-1344
7 Fry DE. Sepis syndrome. Am Surg 2000;66:126-132
8 Erwig LP, Gordon S, Walsh GM, Rees AJ. Previous uptake of apoptotic neutrophils or ligation of integrin receptors
downmodulates the ability of macrophages to ingest apoptotic neutrophils. Blood 1999;93:1406-1412
9 Chitnis D, Dickerson C, Munster AM, Winchurch RA. Inhibition of apoptosis In polymorphonuclear neutrophils from
burn patients. Leukoc Biol 1996;59:835-839
10 Dunican A, Grutkoski P, Leuenroth S, Ayala A, Simms HH. Neutrophils regulate their own apoptosis via preservation
of CXC receptors. J Surg Res 2000;90:32-38
11 Sano J, Oguma K, Kano R, Tsumagari S, Hasegawa A. Decreased apoptotic polymorphonuclear leukocyte rate in
dogs with pyometra. J Vet Med Sci 2004;66:103-105
12 van Zandbergen G, Gieffers J, Kothe H, Rupp J, Bollinger A, Aga E, Klinger M, Brade H, Dalhoff K, Maass M,Solbach W, Laskay T. Chlamydia pneumoniae multiply in neutrophil granulocytes and delay their spontaneous apoptosis.
J Immunol 2004;172:1768-1776
13 Nolan B, Collette H, Baker S, Duffy A, De M, Miller C, Bankey P. Inhibition of neutrophil apptosis after severe trauma
is NF kappabeta dependet. Trauma 2000;48:599-605
14 Milik AM, Buechner-Maxwell VA, Sonstein J, Kim S, Seitzman GD, Beals TF, Curtis JL. Lung lymphocyte elimination
by apoptosis in the murine response to intratracheal particulate antigen. J Clin Invest 1997;99:1082-1091
15 Stockmeyer B, Beyer T, Neuhuber W, Repp R, Kalden JR, Valerius T, Herrmann M. Polymorphonuclear granulocytes
induce antibody-dependent apoptosis in human breast cancer cells. J Immunol 2003;171:5124-5129
16 Gilroy DW, Colville-Nash PR, McMaster S, Sawatzky DA, Willoughby DA, Lawrence T. Inducible cyclooxygenase-derived
15-deoxy(Delta)12-14PGJ2 brings about acute inflammatory resolution in rat pleurisy by inducing neutrophil and
macrophage apoptosis. FASEB J 2003;17:2269-2271
17 Wagner C, Iking-Konert C, Denefleh B, Stegmaier S, Hug F, Hansch GM. Granzyme B and perforin:constitutive
expression in human polymorphonuclear neutrophils. Blood 2004;103:1099-1104
18 Thompson JS. Epidermal groth factor inhibits somatostatin-induced apoptosis. J Surg Res 1999;81:95-100
19 Sener G, Sehirli AO, Satiroglu H, Kacmaz A, Ayanoglu-Dulger G, Yegen BC. Octreotide improves burn-induced
intestinal injury in the rat. Peptides 2003;24:123-127
20 Kobayashi SD, Braughton KR, Whitney AR, Voyich JM, Schwan TG, Musser JM, DeLeo FR. Bacterial pathogens
modulate an apoptosis differentiation program in human neutrophils. Proc Natl Acad Sci USA 2003;100:10948-10953
21 Liu Y, Zhang J, Zhao Z, Ling Y. Pro-apoptotic role of NF-kappaB pathway inhibition in lipopolysaccharide-stimulated
polymorphonuclear neutrophils. Chin Med J (Engl) 2003;116:1257-1261
22 Haslett C. Resolution of acute inflammation and the role of apoptosis in the tissue fate of granulocytes.
Clin Sci (Lond) 2001;83:639-648
23 Liu R, Li SD, Min JX, Xiao N, Jiang QS, Tian KL, Diao YF. PMN apoptosis and its relationship with the lung injury after
chest impact trauma. Chin Med J (Engl) 2004;117:888-892
24 McLoughlin RM, Witowski J, Robson RL, Wilkinson TS, Hurst SM, Williams AS, Williams JD, Rose-John S, Jones SA,Topley N. Interplay between IFN-gamma and IL-6 signaling governs neutrophil trafficking and apoptosis during acute
inflammation. J Clin Invest 2003;112:598-607
25 Solito E, Kamal A, Russo-Marie F, Buckingham JC, Marullo S, Perretti M. A novel calcium-dependent proapoptotic
effect of annexin 1 on human neutrophils. FASEB J 2003;17:1544-1546
26 Reidy MF, Wright JR. Surfactant protein A enhances apoptotic cell uptake and TGF-beta1 release by inflammatory
alveolar macrophages. Am J Physiol Lung Cell Mol Physiol 2003;285:L854-L861
27 Keel M, Ungethum U, Steckholzer U, Niederer E, Hartung T, Trentz O, Ertel W. Interleukin-10 counterregulates
proinflammatory cytokine-induced inhibition of neutrophil apoptosis during severe sepsis. Blood 1997;90:3356-3363
28 Miyazaki S, Ishikawa F, Fujikawa T, Nagata S, Yamaguchi K. Intraperitoneal injection of lipopolysaccharide induces
dynamic migration of Gr-1high polymorphonuclear neutrophils in the murine abdominal cavity. Clin Diagn Lab Immunol
2004;11:452-457
29 Choi M, Rolle S, Wellner M, Cardoso MC, Scheidereit C, Luft FC, Kettritz R. Inhibition of NF-kappaB by a
TAT-NEMO-binding domain peptide accelerates constitutive apoptosis and abrogates LPS-delayed neutrophil
apoptosis. Blood 2003;102:2259-2267
30 Kobayashi SD, Voyich JM, Braughton KR, DeLeo FR. Down-regulation of proinflammatory capacity during apoptosis
in human polymorphonuclear leukocytes. J Immunol 2003;170:3357-3368
31 Goris RJ. MODS/SIRS: result of an overwhelming inflammatory response? World J Surg 1996;20:418-421
编辑 潘伯荣, 百拇医药( 许兰涛,唐承薇)
许兰涛,男, 1964-07-03生, 副主任医师, 副教授, 博士, 主要从事消化内科的研究.
国家自然科学基金资助项目, No. 30170875
项目负责人: 唐承薇, 610041, 四川省成都市, 四川大学华西医院消化内科. sccdlx@sohu.com
电话: 028-85445341
收稿日期: 2004-12-22 接受日期: 2005-01-20
Effect of somstostatin on apoptosis of polymorphonuclear neutrophils of rhesus monkey
Lan-Tao Xu, Cheng-Wei Tang
Lan-Tao Xu, Cheng-Wei Tang, Department of Digestology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Supported by National Science Foundation of China, No.30170875
Correspondence to: Cheng-Wei Tang, Department of Digestology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China. sccdlx@sohu.com
Received: 2004-12-22 Accepted: 2005-01-20
Abstract
AIM: To study the effect of somstostatin on the apoptosis of polymorphonuclear neutrophils (PMNs) in rhesus monkey.
METHODS: PMNs were isolated from whole blood of normal rhesus monkey using one-step discontinuous Percoll gradient centrifugation technique. PMNs were cultured with 5´10-5mol/L somstostatin. Cell morphology was examined by light and electronic microscopy. Apoptosis was detected by flow cytometry and DNA agarose electrophoresis.
RESULTS: Somstostatin at 5´10-5mol/L induced significant apoptosis in PMNs. The cells manifested typical apoptotic morphology: cell membrane blebbing, chromatin condensation, nucleic fragmentation and apoptotic body formation. Agarose electrophoresis revealed specific DNA ladder. Flow cytometry analysis showed that the ratio of PMNs undergoing apoptosis was remarkably increased from 22.1% to 50.5% following somstostatin treatment (P<0.01).
CONCLUSION: Somstostatin induces apoptosis of PMNs in rhesus monkey. It may be a new target for the treatment of multiple organ dysfunction syndrome (MODS).
Key Words: PMN; Apoptosis; Somatostatin; Rhesus monkey; MODS
Xu LT, Tang CW. Effect of somstostatin on apoptosis of polymorphonuclear neutrophils of rhesus monkey. Shijie Huaren Xiaohua Zazhi 2005;13(5):617-620
摘要
目的: 观察生长抑素对猕猴外周血中性粒细胞的作用.
方法: 用生长抑素与猕猴外周血中性粒细胞共同孵育一定时间后,采用流式细胞仪、DNA电泳、电镜观察猕猴外周血中性粒细胞的形态变化,细胞DNA含量分布变化.
结果: 生长抑素能诱导猕猴外周血中性粒细胞凋亡,在形态学上表现为细胞膜起泡、染色质固缩、核碎裂、凋亡小体形成;电泳呈凋亡特征性Ladder带;流式细胞仪分析显示,PMN凋亡比例增高(22.1%vs50.5%. P<0.01).
结论: 生长抑素能诱导猕猴外周血中性粒细胞凋亡.
关键词: 猕猴; 生长抑素; 中性粒细胞; 凋亡; 多器官功能衰竭
许兰涛, 唐承薇. 生长抑素诱导猕猴外周血中性粒细胞凋亡. 世界华人消化杂志 2005;13(5):617-620
:无凋亡图; B:凋亡.
表1 不同浓度生长抑素对PMN凋亡率的影响
组别 | 凋亡率(%) | |
1 | 对照组 | 22.1±0.28 |
2 | ss (5×10-6 mol/L) | 33.6±0.52 |
3 | ss (5×10-5 mol/L) | 50.5±0.56 |
P<0.01vs对照组.
2.3 DNA电泳结果 将5´108/L PMN细胞与5´10-5 mol/L生长抑素作用30 min,DNA电泳呈明显凋亡带,对照组则无凋亡带(图2).
图2 (PDF) DNA电泳Ladder带.
2.4 电镜观察 将5´108/L PMN细胞与5´10-5 mol/L生长抑素作用30 min,电镜下可见染色质固缩,聚集于核膜下成块状,胞核固缩,染色质凝集,细胞质浓缩,部分细胞碎裂成片,形成质膜包被的大小不等的凋亡小体(图3).
图3 中性粒细包超微结构TEM×8000.A: 正常; B:凋亡; C:凋亡小体.
3 讨论由于分子生物学发展,尤其是抗炎症递质治疗在临床应用中并不理想后,国内外学者转向炎症递质调控凋亡的研究,就凋亡和MODS发生机制作了新的探讨.Haslett[22-26]提出炎症反应的失调与中性粒细胞凋亡比率有关.Keel[27-30]在MODS研究中发现外周血中中性粒细胞(PMN)凋亡延迟,并且血中有抗凋亡因子存在.认为凋亡延迟引起PMN寿命延长可能与MODS发生有关.Goris[31]提出经过特异性细胞因子触发凋亡可以解释进行性过度炎症反应可以发展到MODS的最后假说.
目前已经明确MODS是过度炎症反应的结果,在创伤后有MODS高风险的患者中,PMN凋亡延迟,血浆中的递质使PMN凋亡延迟,并且PMN的作用引发过度炎症反应及器官损伤,创伤后PMN的凋亡在MODS的发生发展中可能具有重要作用.凋亡区别于坏死的重要之处是凋亡的细胞能被巨噬细胞或周围组织细胞平稳识别、清除而不引发炎症反应,因此有研究认为通过凋亡方式清除炎症部位的PMN是限制组织损伤,促进炎症吸收的重要机制.识别清除凋亡PMN的能力降低,大量凋亡的PMN不能被及时有效地处理而裂解坏死,炎症不易控制,因此这种损伤很容易导致MODS.本实验研究表明:生长抑素能诱导中性粒细胞凋亡,可以减少氧自由基、蛋白酶和炎性递质的释放,有利于巨噬细胞的吞噬,必将为治疗MODS开辟新的领域.
4 参考文献1 Diamond RD, Clark RA, Haudenschild CC. Damage to Candida albicans hyphae and pseudohyphae by the
myeloperoxidase system and oxidative products of neutrophil metabolism in vitro. J Clin Invest 1980;66:908-917
2 Sweeney JF, Nguyen PK, Omann G, Hinshaw DB. Granulocyte-macrophage colony-stimulating factor rescues human
polymorphonuclear leukocytes from ultraviolet irradiation-accelerated apoptosis. J Surg Res 1999;81:108-112
3 Suzuki K, Hasegawa T, Sakamato C, Zhou YM, Hato F, Hino M, Tatsumi N, Kitagawa S. Cleavage of mitogen-activated
protein kinases in human neutrophils undergoing-apoptosis: Role in decreased responsiveness to inflammatory cytokines.
J Immunol 2001;166:1185-1192
4 Sweeney JF, Nguyen PK, Hinshaw DB. Caspase-3 inhibition partially protects oxidant production in apoptotic human
neutrophils. J Surg Res 2001;98:66-70
5 Sun XM, MacFarlane M, Zhuang J, Wolf BB, Green DR, Cohen GM. Distinct caspase cascades are initiated in receptor
mediated and chemical induced apoptosis. J Biol Chem 1999;274:5053-5060
6 Kobayashi SD, Voyich JM, DeLeo FR. Regulation of the neutrophil-mediated inflammatory response to infection.
Microbes Infect 2003;5:1337-1344
7 Fry DE. Sepis syndrome. Am Surg 2000;66:126-132
8 Erwig LP, Gordon S, Walsh GM, Rees AJ. Previous uptake of apoptotic neutrophils or ligation of integrin receptors
downmodulates the ability of macrophages to ingest apoptotic neutrophils. Blood 1999;93:1406-1412
9 Chitnis D, Dickerson C, Munster AM, Winchurch RA. Inhibition of apoptosis In polymorphonuclear neutrophils from
burn patients. Leukoc Biol 1996;59:835-839
10 Dunican A, Grutkoski P, Leuenroth S, Ayala A, Simms HH. Neutrophils regulate their own apoptosis via preservation
of CXC receptors. J Surg Res 2000;90:32-38
11 Sano J, Oguma K, Kano R, Tsumagari S, Hasegawa A. Decreased apoptotic polymorphonuclear leukocyte rate in
dogs with pyometra. J Vet Med Sci 2004;66:103-105
12 van Zandbergen G, Gieffers J, Kothe H, Rupp J, Bollinger A, Aga E, Klinger M, Brade H, Dalhoff K, Maass M,Solbach W, Laskay T. Chlamydia pneumoniae multiply in neutrophil granulocytes and delay their spontaneous apoptosis.
J Immunol 2004;172:1768-1776
13 Nolan B, Collette H, Baker S, Duffy A, De M, Miller C, Bankey P. Inhibition of neutrophil apptosis after severe trauma
is NF kappabeta dependet. Trauma 2000;48:599-605
14 Milik AM, Buechner-Maxwell VA, Sonstein J, Kim S, Seitzman GD, Beals TF, Curtis JL. Lung lymphocyte elimination
by apoptosis in the murine response to intratracheal particulate antigen. J Clin Invest 1997;99:1082-1091
15 Stockmeyer B, Beyer T, Neuhuber W, Repp R, Kalden JR, Valerius T, Herrmann M. Polymorphonuclear granulocytes
induce antibody-dependent apoptosis in human breast cancer cells. J Immunol 2003;171:5124-5129
16 Gilroy DW, Colville-Nash PR, McMaster S, Sawatzky DA, Willoughby DA, Lawrence T. Inducible cyclooxygenase-derived
15-deoxy(Delta)12-14PGJ2 brings about acute inflammatory resolution in rat pleurisy by inducing neutrophil and
macrophage apoptosis. FASEB J 2003;17:2269-2271
17 Wagner C, Iking-Konert C, Denefleh B, Stegmaier S, Hug F, Hansch GM. Granzyme B and perforin:constitutive
expression in human polymorphonuclear neutrophils. Blood 2004;103:1099-1104
18 Thompson JS. Epidermal groth factor inhibits somatostatin-induced apoptosis. J Surg Res 1999;81:95-100
19 Sener G, Sehirli AO, Satiroglu H, Kacmaz A, Ayanoglu-Dulger G, Yegen BC. Octreotide improves burn-induced
intestinal injury in the rat. Peptides 2003;24:123-127
20 Kobayashi SD, Braughton KR, Whitney AR, Voyich JM, Schwan TG, Musser JM, DeLeo FR. Bacterial pathogens
modulate an apoptosis differentiation program in human neutrophils. Proc Natl Acad Sci USA 2003;100:10948-10953
21 Liu Y, Zhang J, Zhao Z, Ling Y. Pro-apoptotic role of NF-kappaB pathway inhibition in lipopolysaccharide-stimulated
polymorphonuclear neutrophils. Chin Med J (Engl) 2003;116:1257-1261
22 Haslett C. Resolution of acute inflammation and the role of apoptosis in the tissue fate of granulocytes.
Clin Sci (Lond) 2001;83:639-648
23 Liu R, Li SD, Min JX, Xiao N, Jiang QS, Tian KL, Diao YF. PMN apoptosis and its relationship with the lung injury after
chest impact trauma. Chin Med J (Engl) 2004;117:888-892
24 McLoughlin RM, Witowski J, Robson RL, Wilkinson TS, Hurst SM, Williams AS, Williams JD, Rose-John S, Jones SA,Topley N. Interplay between IFN-gamma and IL-6 signaling governs neutrophil trafficking and apoptosis during acute
inflammation. J Clin Invest 2003;112:598-607
25 Solito E, Kamal A, Russo-Marie F, Buckingham JC, Marullo S, Perretti M. A novel calcium-dependent proapoptotic
effect of annexin 1 on human neutrophils. FASEB J 2003;17:1544-1546
26 Reidy MF, Wright JR. Surfactant protein A enhances apoptotic cell uptake and TGF-beta1 release by inflammatory
alveolar macrophages. Am J Physiol Lung Cell Mol Physiol 2003;285:L854-L861
27 Keel M, Ungethum U, Steckholzer U, Niederer E, Hartung T, Trentz O, Ertel W. Interleukin-10 counterregulates
proinflammatory cytokine-induced inhibition of neutrophil apoptosis during severe sepsis. Blood 1997;90:3356-3363
28 Miyazaki S, Ishikawa F, Fujikawa T, Nagata S, Yamaguchi K. Intraperitoneal injection of lipopolysaccharide induces
dynamic migration of Gr-1high polymorphonuclear neutrophils in the murine abdominal cavity. Clin Diagn Lab Immunol
2004;11:452-457
29 Choi M, Rolle S, Wellner M, Cardoso MC, Scheidereit C, Luft FC, Kettritz R. Inhibition of NF-kappaB by a
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编辑 潘伯荣, 百拇医药( 许兰涛,唐承薇)