臺灣博碩士論文加值系統

嗜中性白血球長久以來已被認為和急性發炎反應有著重要關係，但是最近越來越多的研究證據證實了嗜中性白血球也確實參與在慢性發炎過程中。許多急性和慢性發炎疾病，如：心肌缺血再灌流傷害、敗血症以及慢性阻塞性肺病等，都和嗜中性白血球浸潤與過度活化有關。甲醯化胜肽是透過和嗜中性白血球上的甲醯化胜肽受體 (formyl peptide receptor1, FPR1) 結合，啟動了發炎反應，基於FPR1 在細菌性和無菌性發炎反應的重要性，所以近來逐漸被視為抗發炎藥物發展新標的。Propofol (其主成分為2,6-diisopropylphenol, 異丙酚) 是一種臨床廣泛作為靜脈注射麻醉藥，眾多在動物和人體的研究證明，異丙酚在發炎反應過程中發揮了保護的作用。雖然有非常多的研究探討異丙酚的作用以及機轉，但是卻也留下更多重要的疑問。在本論文中，我們觀察到異丙酚對於以N-formylmethionyl-leucyl-phenylalanine (fMLF) 活化人類嗜中性白血球的趨化性、釋放超氧自由基及彈性蛋白酶的作用有顯著降低的能力。本論文同時呈現異丙酚在無細胞系統中不具改變超氧自由基產生和影響彈性蛋白酶活性等的作用。而這些異丙酚所造成的抑制作用，並非由GABA受體或protein kinase A路徑所調控。有趣的是，若是以其他非FPR1刺激劑活化嗜中性白血球時，異丙酚抑制效果明顯變差。此外異丙酚具有競爭性抑制甲醯化胜肽受體下游訊號傳導路徑如calcium、Akt、Erk1/2等現象，這些結果都暗示異丙酚的抑制作用是專一性且競爭性的針對特定刺激劑--fMLF所活化的嗜中性白血球而來，重要地，在接受體實驗中，異丙酚可以阻斷fMLF的發螢光類似物--N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein
，結合到FPR1的作用。並且這種抑制現象也同時出現在分化的THP-1 monocytes上以及轉殖FPR1基因的HEK293細胞上。根據本論文結果顯示，異丙酚透過競爭性阻斷嗜中性白血球細胞膜上FPR1而有抗發炎的功效。就目前所知，這將是第一個提出異丙酚是一個甲醯化胜肽受體選擇性抑制劑的研究。因為甲醯化胜肽在發炎性疾病扮演了重要的角色，所以本論文中指出異丙酚具有成為抑制甲醯化胜肽活化嗜中性白血球所導致發炎性疾病的新藥理用途的潛力。

Neutrophils play a critical role in acute and chronic inflammatory processes, including myocardial ischemia/reperfusion injury, sepsis, and adult respiratory distress syndrome. Binding of formyl peptide receptor 1 (FPR1) by N-formyl peptides can activate neutrophils and may represent a new therapeutic target in either sterile or septic inflammation. Propofol, a widely used i.v. anesthetic, has been shown to modulate immunoinflammatory responses. However, the mechanism of propofol remains to be established. In this study, we showed that propofol significantly reduced superoxide generation, elastase release and chemotaxis in human neutrophils activated by N-formylmethionyl-leucyl-phenylalanine (fMLF). Propofol did not alter superoxide generation or elastase release in a cell-free system. Neither inhibitors of GABA receptors nor an inhibitor of protein kinase A reversed the inhibitory effects of propofol. Interestingly, propofol showed less inhibitory effects in non-FPR1-induced cell responses. The signaling pathways downstream from FPR1, involving calcium, Akt, and Erk1/2, were also competitively inhibited by propofol. These results show that propofol selectively and competitively inhibits the FPR1-induced human neutrophil activation. Consistent with the hypothesis, propofol inhibited the binding of N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein, a fluorescent analogue of fMLF, to FPR1 in human neutrophils, differentiated THP-1 cells, and FPR1-transfected human embryonic kidney 293 cells. Our results identify, for the first time, a novel anti-inflammatory mechanism of propofol by competitively blocking FPR1 in human neutrophils. Considering the importance of N-formyl peptides in inflammatory processes, our data indicate that propofol may have therapeutic potential to attenuate neutrophil-mediated inflammatory diseases by blocking FPR1.

指導教授推薦書 i
口試委員審定書 ii
長庚大學碩士論文著作授權書 iii
誌謝 iv
縮寫表 v
中文摘要 vii
Abstract viii
目錄 ix
第一章 緒論 1
1.1 前言 1
1.2 異丙酚的介紹 2
1.3 人類嗜中性白血球免疫功能的介紹 4
1.4 FPR的介紹 6
1.5 人類嗜中性白血球細胞內調控免疫功能的相關訊息傳導路徑 9
第二章 實驗材料與方法 13
2.1 實驗材料 13
2.2 人類嗜中性白血球製備 13
2.3 THP-1細胞製備 14
2.4 HEK293細胞株培養以及FPR1基因轉殖 14
2.5 細胞存活率 (cell viability) 判定 14
2.6 活性氧自由基釋放測定 14
2.7 細胞外自由基清除能力測定 16
2.8 Lactate dehydrogenase (LDH) 細胞毒性測試 16
2.9 彈性蛋白酶釋放量測定 16
2.10 細胞趨化性測試 17
2.11 cAMP 含量測定 17
2.12 細胞內Ca2+濃度測定 18
2.13 接受體結合測定 18
2.14 西方點墨法 18
2.15 統計方法 19
第三章 實驗結果 20
3.1 探討異丙酚對於fMLF刺激下人類嗜中性白血球產生超氧自由基的影響 20
3.2 探討異丙酚對於fMLF刺激下人類嗜中性白血球產生彈性蛋白酶的影響 20
3.4 探討異丙酚在無細胞系統下對於活性氧自由基以及彈性蛋白酶的影響 21
3.5 探討異丙酚對於不同刺激劑刺激下人類嗜中性白血球產生超氧自由基和彈性蛋白酶的影響 21
3.6 探討異丙酚對於人類嗜中性白血球趨化性的影響 22
3.7 探討異丙酚對於人類嗜中性白血球上FPR1功能的影響 23
3.8 探討異丙酚對於fMLF刺激下人類嗜中性白血球產生超氧自由基和彈性蛋白酶的競爭性抑制作用 23
3.9 探討GABAA或GABAB受體對於fMLF刺激下人類嗜中性白血球功能的影響 24
3.10 探討cAMP/ Protein kinase A pathway 對異丙酚處理後fMLF刺激下人類嗜中性白血球功能的影響 24
3.11 探討異丙酚抑制人類嗜中性白血球功能是否藉由抑制protein phosphotase的相關路徑而來 25
3.12 異丙酚對於fMLF刺激下人類嗜中性白血球內Ca2+濃度的變化 25
3.13 異丙酚對於非FPR1刺激劑刺激下人類嗜中性白血球內Ca2+濃度的變化 25
3.14 觀察異丙酚對於fMLF刺激下人類嗜中性白血球mitogen-activated protein kinases (MAP kinases) 的影響 25
3.15 觀察異丙酚對於fMLF刺激下人類嗜中性白血球Akt的影響 26
3.16 觀察在分化後THP-1細胞異丙酚對於FPR1受體結合的影響 26
3.17 異丙酚對於活化分化後THP-1細胞內Ca2+濃度的影響 26
3.18 觀察在轉殖FPR1基因的HEK293細胞中異丙酚對於FPR1受體結合的影響 26
第四章 討論 28
第五章 圖表 32
參考文獻 68

Abraham E (2003) Neutrophils and acute lung injury. Crit Care Med 31(4 Suppl):S195-199.
Alam S, Laughton DL, Walding A and Wolstenholme AJ (2006) Human peripheral blood mononuclear cells express GABAA receptor subunits. Mol Immunol 43(9):1432-1442.
Amulic B, Cazalet C, Hayes GL, Metzler KD and Zychlinsky A (2012) Neutrophil function: from mechanisms to disease. Annu Rev Immunol 30:459-489.
An K, Shu H, Huang W, Huang X, Xu M, Yang L, Xu K and Wang C (2008) Effects of propofol on pulmonary inflammatory response and dysfunction induced by cardiopulmonary bypass. Anaesthesia 63(11):1187-1192.
Anderson R, Theron AJ, Gravett CM, Steel HC, Tintinger GR and Feldman C (2009) Montelukast inhibits neutrophil pro-inflammatory activity by a cAMP-dependent mechanism. Br J Pharmacol 156(1):105-115.
Aoki K, Yamada M, Kunida K, Yasuda S and Matsuda M (2011) Processive phosphorylation of ERK MAP kinase in mammalian cells. Proc Natl Acad Sci U S A 108(31):12675-12680.
Arnoult D, Soares F, Tattoli I and Girardin SE (2011) Mitochondria in innate immunity. EMBO Rep 12(9):901-910.
Bao YP, Williamson G, Tew D, Plumb GW, Lambert N, Jones JG and Menon DK (1998) Antioxidant effects of propofol in human hepatic microsomes: concentration effects and clinical relevance. Br J Anaesth 81(4):584-589.
Barr J, Fraser GL, Puntillo K, Ely EW, Gelinas C, Dasta JF, Davidson JE, Devlin JW, Kress JP, Joffe AM, Coursin DB, Herr DL, Tung A, Robinson BR, Fontaine DK, Ramsay MA, Riker RR, Sessler CN, Pun B, Skrobik Y and Jaeschke R (2013) Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med 41(1):263-306.
Bhat R, Axtell R, Mitra A, Miranda M, Lock C, Tsien RW and Steinman L (2010) Inhibitory role for GABA in autoimmune inflammation. Proc Natl Acad Sci U S A 107(6):2580-2585.
Brazil DP and Hemmings BA (2001) Ten years of protein kinase B signalling: a hard Akt to follow. Trends Biochem Sci 26(11):657-664.
Brechard S and Tschirhart EJ (2008) Regulation of superoxide production in neutrophils: role of calcium influx. J Leukoc Biol 84(5):1223-1237.
Carp H (1982) Mitochondrial N-formylmethionyl proteins as chemoattractants for neutrophils. J Exp Med 155(1):264-275.
Cevik-Aras H, Kalderen C, Jenmalm Jensen A, Oprea T, Dahlgren C and Forsman H (2012) A non-peptide receptor inhibitor with selectivity for one of the neutrophil formyl peptide receptors, FPR 1. Biochem Pharmacol 83(12):1655-1662.
Chan KC, Lin CJ, Lee PH, Chen CF, Lai YL, Sun WZ and Cheng YJ (2008) Propofol attenuates the decrease of dynamic compliance and water content in the lung by decreasing oxidative radicals released from the reperfused liver. Anesth Analg 107(4):1284-1289.
Chen HI, Hsieh NK, Kao SJ and Su CF (2008) Protective effects of propofol on acute lung injury induced by oleic acid in conscious rats. Crit Care Med 36(4):1214-1221.
Chen J, Tang H, Hay N, Xu J and Ye RD (2010) Akt isoforms differentially regulate neutrophil functions. Blood 115(21):4237-4246.
Chen Q, Powell DW, Rane MJ, Singh S, Butt W, Klein JB and McLeish KR (2003a) Akt phosphorylates p47phox and mediates respiratory burst activity in human neutrophils. J Immunol 170(10):5302-5308.
Chen RM, Wu CH, Chang HC, Wu GJ, Lin YL, Sheu JR and Chen TL (2003b) Propofol suppresses macrophage functions and modulates mitochondrial membrane potential and cellular adenosine triphosphate synthesis. Anesthesiology 98(5):1178-1185.
Cheng YJ, Wang YP, Chien CT and Chen CF (2002) Small-dose propofol sedation attenuates the formation of reactive oxygen species in tourniquet-induced ischemia-reperfusion injury under spinal anesthesia. Anesth Analg 94(6):1617-1620, table of contents.
Christophe T, Karlsson A, Dugave C, Rabiet MJ, Boulay F and Dahlgren C (2001) The synthetic peptide Trp-Lys-Tyr-Met-Val-Met-NH2 specifically activates neutrophils through FPRL1/lipoxin A4 receptors and is an agonist for the orphan monocyte-expressed chemoattractant receptor FPRL2. J Biol Chem 276(24):21585-21593.
Concas A, Santoro G, Serra M, Sanna E and Biggio G (1991) Neurochemical action of the general anaesthetic propofol on the chloride ion channel coupled with GABAA receptors. Brain Res 542(2):225-232.
Cooper DM and Crossthwaite AJ (2006) Higher-order organization and regulation of adenylyl cyclases. Trends Pharmacol Sci 27(8):426-431.
Corcoran TB, Engel A, Sakamoto H, O'Callaghan-Enright S, O'Donnell A, Heffron JA and Shorten G (2004) The effects of propofol on lipid peroxidation and inflammatory response in elective coronary artery bypass grafting. J Cardiothorac Vasc Anesth 18(5):592-604.
Corcoran TB, Engel A, Sakamoto H, O'Shea A, O'Callaghan-Enright S and Shorten GD (2006) The effects of propofol on neutrophil function, lipid peroxidation and inflammatory response during elective coronary artery bypass grafting in patients with impaired ventricular function. Br J Anaesth 97(6):825-831.
Cowburn AS, Condliffe AM, Farahi N, Summers C and Chilvers ER (2008) Advances in neutrophil biology: clinical implications. Chest 134(3):606-612.
Crouser ED, Shao G, Julian MW, Macre JE, Shadel GS, Tridandapani S, Huang Q and Wewers MD (2009) Monocyte activation by necrotic cells is promoted by mitochondrial proteins and formyl peptide receptors. Crit Care Med 37(6):2000-2009.
Dahlgren C, Christophe T, Boulay F, Madianos PN, Rabiet MJ and Karlsson A (2000) The synthetic chemoattractant Trp-Lys-Tyr-Met-Val-DMet activates neutrophils preferentially through the lipoxin A(4) receptor. Blood 95(5):1810-1818.
Dahlgren C and Karlsson A (1999) Respiratory burst in human neutrophils. J Immunol Methods 232(1-2):3-14.
Davidson JA, Boom SJ, Pearsall FJ, Zhang P and Ramsay G (1995) Comparison of the effects of four i.v. anaesthetic agents on polymorphonuclear leucocyte function. Br J Anaesth 74(3):315-318.
Demiryurek AT, Cinel I, Kahraman S, Tecder-Unal M, Gogus N, Aypar U and Kanzik I (1998) Propofol and intralipid interact with reactive oxygen species: a chemiluminescence study. Br J Anaesth 80(5):649-654.
Dessauer CW (2009) Adenylyl cyclase--A-kinase anchoring protein complexes: the next dimension in cAMP signaling. Mol Pharmacol 76(5):935-941.
Doze VA, Westphal LM and White PF (1986) Comparison of propofol with methohexital for outpatient anesthesia. Anesth Analg 65(11):1189-1195.
El-Benna J, Dang PM, Gougerot-Pocidalo MA, Marie JC and Braut-Boucher F (2009) p47phox, the phagocyte NADPH oxidase/NOX2 organizer: structure, phosphorylation and implication in diseases. Exp Mol Med 41(4):217-225.
English D, Roloff JS and Lukens JN (1981) Chemotactic factor enhancement of superoxide release from fluoride and phorbol myristate acetate stimulated neutrophils. Blood 58(1):129-134.
Ernst S, Lange C, Wilbers A, Goebeler V, Gerke V and Rescher U (2004) An annexin 1 N-terminal peptide activates leukocytes by triggering different members of the formyl peptide receptor family. J Immunol 172(12):7669-7676.
Erol A, Reisli R, Reisli I, Kara R and Otelcioglu S (2009) Effects of desflurane, sevoflurane and propofol on phagocytosis and respiratory burst activity of human polymorphonuclear leucocytes in bronchoalveolar lavage. Eur J Anaesthesiol 26(2):150-154.
Ferguson GJ, Milne L, Kulkarni S, Sasaki T, Walker S, Andrews S, Crabbe T, Finan P, Jones G, Jackson S, Camps M, Rommel C, Wymann M, Hirsch E, Hawkins P and Stephens L (2007) PI(3)Kgamma has an important context-dependent role in neutrophil chemokinesis. Nat Cell Biol 9(1):86-91.
Forsman H, Andreasson E, Karlsson J, Boulay F, Rabiet MJ and Dahlgren C (2012) Structural characterization and inhibitory profile of formyl peptide receptor 2 selective peptides descending from a PIP2-binding domain of gelsolin. J Immunol 189(2):629-637.
Frohlich D, Rothe G, Schwall B, Schmitz G, Hobbhahn J and Taeger K (1996) Thiopentone and propofol, but not methohexitone nor midazolam, inhibit neutrophil oxidative responses to the bacterial peptide FMLP. Eur J Anaesthesiol 13(6):582-588.
Frohlich D, Trabold B, Rothe G, Hoerauf K and Wittmann S (2006) Inhibition of the neutrophil oxidative response by propofol: preserved in vivo function despite in vitro inhibition. Eur J Anaesthesiol 23(11):948-953.
Fruman DA (2011) Phosphoinositide 3-kinases. Transduction Mechanisms in Cellular Signaling: Cell Signaling Collection:275.
Galley HF, Dubbels AM and Webster NR (1998) The effect of midazolam and propofol on interleukin-8 from human polymorphonuclear leukocytes. Anesth Analg 86(6):1289-1293.
Gao J, Zeng BX, Zhou LJ and Yuan SY (2004) Protective effects of early treatment with propofol on endotoxin-induced acute lung injury in rats. Br J Anaesth 92(2):277-279.
Gaudreault E, Thompson C, Stankova J and Rola-Pleszczynski M (2005) Involvement of BLT1 endocytosis and Yes kinase activation in leukotriene B4-induced neutrophil degranulation. J Immunol 174(6):3617-3625.
Gavins FN (2010) Are formyl peptide receptors novel targets for therapeutic intervention in ischaemia-reperfusion injury? Trends Pharmacol Sci 31(6):266-276.
Grinstein S and Furuya W (1988) Receptor-mediated activation of electropermeabilized neutrophils. Evidence for a Ca2+- and protein kinase C-independent signaling pathway. J Biol Chem 263(4):1779-1783.
Grommes J and Soehnlein O (2011) Contribution of neutrophils to acute lung injury. Mol Med 17(3-4):293-307.
Gulcin I, Alici HA and Cesur M (2005) Determination of in vitro antioxidant and radical scavenging activities of propofol. Chem Pharm Bull (Tokyo) 53(3):281-285.
Hauser CJ, Sursal T, Rodriguez EK, Appleton PT, Zhang Q and Itagaki K (2010) Mitochondrial damage associated molecular patterns from femoral reamings activate neutrophils through formyl peptide receptors and P44/42 MAP kinase. J Orthop Trauma 24(9):534-538.
Hirsch E, Katanaev VL, Garlanda C, Azzolino O, Pirola L, Silengo L, Sozzani S, Mantovani A, Altruda F and Wymann MP (2000) Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation. Science 287(5455):1049-1053.
Hofbauer R, Frass M, Salfinger H, Moser D, Hornykewycz S, Gmeiner B and Kapiotis S (1999) Propofol reduces the migration of human leukocytes through endothelial cell monolayers. Crit Care Med 27(9):1843-1847.
Hommes DW, Peppelenbosch MP and van Deventer SJ (2003) Mitogen activated protein (MAP) kinase signal transduction pathways and novel anti-inflammatory targets. Gut 52(1):144-151.
Hsing CH, Lin MC, Choi PC, Huang WC, Kai JI, Tsai CC, Cheng YL, Hsieh CY, Wang CY, Chang YP, Chen YH, Chen CL and Lin CF (2011) Anesthetic propofol reduces endotoxic inflammation by inhibiting reactive oxygen species-regulated Akt/IKKbeta/NF-kappaB signaling. PLoS One 6(3):e17598.
Hu JY, Le Y, Gong W, Dunlop NM, Gao JL, Murphy PM and Wang JM (2001) Synthetic peptide MMK-1 is a highly specific chemotactic agonist for leukocyte FPRL1. J Leukoc Biol 70(1):155-161.
Huang C, Jacobson K and Schaller MD (2004) MAP kinases and cell migration. J Cell Sci 117(Pt 20):4619-4628.
Hwang TL, Li GL, Lan YH, Chia YC, Hsieh PW, Wu YH and Wu YC (2009a) Potent inhibition of superoxide anion production in activated human neutrophils by isopedicin, a bioactive component of the Chinese medicinal herb Fissistigma oldhamii. Free Radic Biol Med 46(4):520-528.
Hwang TL, Su YC, Chang HL, Leu YL, Chung PJ, Kuo LM and Chang YJ (2009b) Suppression of superoxide anion and elastase release by C18 unsaturated fatty acids in human neutrophils. J Lipid Res 50(7):1395-1408.
Hwang TL, Wang CC, Kuo YH, Huang HC, Wu YC, Kuo LM and Wu YH (2010) The hederagenin saponin SMG-1 is a natural FMLP receptor inhibitor that suppresses human neutrophil activation. Biochem Pharmacol 80(8):1190-1200.
Ishibashi K, Okazaki S and Hiramatsu M (2006) Simultaneous measurement of superoxide generation and intracellular Ca2+ concentration reveals the effect of extracellular Ca2+ on rapid and transient contents of superoxide generation in differentiated THP-1 cells. Biochem Biophys Res Commun 344(2):571-580.
Ishihara H, Martin BL, Brautigan DL, Karaki H, Ozaki H, Kato Y, Fusetani N, Watabe S, Hashimoto K, Uemura D and et al. (1989) Calyculin A and okadaic acid: inhibitors of protein phosphatase activity. Biochem Biophys Res Commun 159(3):871-877.
Ito Y and Lipschitz DA (2002) Assay of intracellular hydrogen peroxide generation in activated individual neutrophils by flow cytometry. Methods Mol Biol 196:111-116.
Janeway CA, Jr. (1989) Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol 54 Pt 1:1-13.
Jensen AG, Dahlgren C and Eintrei C (1993) Propofol decreases random and chemotactic stimulated locomotion of human neutrophils in vitro. Br J Anaesth 70(1):99-100.
Jordan JE, Zhao ZQ and Vinten-Johansen J (1999) The role of neutrophils in myocardial ischemia-reperfusion injury. Cardiovasc Res 43(4):860-878.
Kampe M, Lampinen M, Stolt I, Janson C, Stalenheim G and Carlson M (2012) PI3-kinase regulates eosinophil and neutrophil degranulation in patients with allergic rhinitis and allergic asthma irrespective of allergen challenge model. Inflammation 35(1):230-239.
Karlsson J, Stenfeldt AL, Rabiet MJ, Bylund J, Forsman HF and Dahlgren C (2009) The FPR2-specific ligand MMK-1 activates the neutrophil NADPH-oxidase, but triggers no unique pathway for opening of plasma membrane calcium channels. Cell Calcium 45(5):431-438.
Ko SH, Yu CW, Lee SK, Choe H, Chung MJ, Kwak YG, Chae SW and Song HS (1997) Propofol attenuates ischemia-reperfusion injury in the isolated rat heart. Anesth Analg 85(4):719-724.
Kokita N, Hara A, Abiko Y, Arakawa J, Hashizume H and Namiki A (1998) Propofol improves functional and metabolic recovery in ischemic reperfused isolated rat hearts. Anesth Analg 86(2):252-258.
Kono H and Rock KL (2008) How dying cells alert the immune system to danger. Nat Rev Immunol 8(4):279-289.
Kotani Y, Shimazawa M, Yoshimura S, Iwama T and Hara H (2008) The experimental and clinical pharmacology of propofol, an anesthetic agent with neuroprotective properties. CNS Neurosci Ther 14(2):95-106.
Krumholz W, Endrass J and Hempelmann G (1994) Propofol inhibits phagocytosis and killing of Staphylococcus aureus and Escherichia coli by polymorphonuclear leukocytes in vitro. Can J Anaesth 41(5 Pt 1):446-449.
Krysko DV, Agostinis P, Krysko O, Garg AD, Bachert C, Lambrecht BN and Vandenabeele P (2011) Emerging role of damage-associated molecular patterns derived from mitochondria in inflammation. Trends Immunol 32(4):157-164.
Kumar V and Sharma A (2010) Neutrophils: Cinderella of innate immune system. Int Immunopharmacol 10(11):1325-1334.
Le Y, Murphy PM and Wang JM (2002) Formyl-peptide receptors revisited. Trends Immunol 23(11):541-548.
Le Y, Oppenheim JJ and Wang JM (2001) Pleiotropic roles of formyl peptide receptors. Cytokine Growth Factor Rev 12(1):91-105.
Mahadeo DC, Janka-Junttila M, Smoot RL, Roselova P and Parent CA (2007) A chemoattractant-mediated Gi-coupled pathway activates adenylyl cyclase in human neutrophils. Mol Biol Cell 18(2):512-522.
Mantovani A, Cassatella MA, Costantini C and Jaillon S (2011) Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol 11(8):519-531.
Marasco WA, Phan SH, Krutzsch H, Showell HJ, Feltner DE, Nairn R, Becker EL and Ward PA (1984) Purification and identification of formyl-methionyl-leucyl-phenylalanine as the major peptide neutrophil chemotactic factor produced by Escherichia coli. J Biol Chem 259(9):5430-5439.
Marik PE (2005) Propofol: an immunomodulating agent. Pharmacotherapy 25(5 Pt 2):28S-33S.
Marques PE, Amaral SS, Pires DA, Nogueira LL, Soriani FM, Lima BH, Lopes GA, Russo RC, Avila TV, Melgaco JG, Oliveira AG, Pinto MA, Lima CX, De Paula AM, Cara DC, Leite MF, Teixeira MM and Menezes GB (2012) Chemokines and mitochondrial products activate neutrophils to amplify organ injury during mouse acute liver failure. Hepatology 56(5):1971-1982.
Matzinger P (1994) Tolerance, danger, and the extended family. Annu Rev Immunol 12:991-1045.
Mayadas TN, Tsokos GC and Tsuboi N (2009) Mechanisms of immune complex-mediated neutrophil recruitment and tissue injury. Circulation 120(20):2012-2024.
McDonald B, Pittman K, Menezes GB, Hirota SA, Slaba I, Waterhouse CC, Beck PL, Muruve DA and Kubes P (2010) Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science 330(6002):362-366.
McHugh D, Tanner C, Mechoulam R, Pertwee RG and Ross RA (2008) Inhibition of human neutrophil chemotaxis by endogenous cannabinoids and phytocannabinoids: evidence for a site distinct from CB1 and CB2. Mol Pharmacol 73(2):441-450.
Migeotte I, Communi D and Parmentier M (2006) Formyl peptide receptors: a promiscuous subfamily of G protein-coupled receptors controlling immune responses. Cytokine Growth Factor Rev 17(6):501-519.
Migeotte I, Riboldi E, Franssen JD, Gregoire F, Loison C, Wittamer V, Detheux M, Robberecht P, Costagliola S, Vassart G, Sozzani S, Parmentier M and Communi D (2005) Identification and characterization of an endogenous chemotactic ligand specific for FPRL2. J Exp Med 201(1):83-93.
Mikawa K, Akamatsu H, Nishina K, Shiga M, Maekawa N, Obara H and Niwa Y (1998) Propofol inhibits human neutrophil functions. Anesth Analg 87(3):695-700.
Momose H, Kurosu H, Tsujimoto N, Kontani K, Tsujita K, Nishina H and Katada T (2003) Dual phosphorylation of phosphoinositide 3-kinase adaptor Grb2-associated binder 2 is responsible for superoxide formation synergistically stimulated by Fc gamma and formyl-methionyl-leucyl-phenylalanine receptors in differentiated THP-1 cells. J Immunol 171(8):4227-4234.
Murphy PG, Ogilvy AJ and Whiteley SM (1996) The effect of propofol on the neutrophil respiratory burst. Eur J Anaesthesiol 13(5):471-473.
Nadel JA (2000) Role of neutrophil elastase in hypersecretion during COPD exacerbations, and proposed therapies. Chest 117(5 Suppl 2):386S-389S.
Nagata T, Kansha M, Irita K and Takahashi S (2001) Propofol inhibits FMLP-stimulated phosphorylation of p42 mitogen-activated protein kinase and chemotaxis in human neutrophils. Br J Anaesth 86(6):853-858.
Obata T, Brown GE and Yaffe MB (2000) MAP kinase pathways activated by stress: the p38 MAPK pathway. Crit Care Med 28(4 Suppl):N67-77.
Palmblad J, Malmsten CL, Uden AM, Radmark O, Engstedt L and Samuelsson B (1981) Leukotriene B4 is a potent and stereospecific stimulator of neutrophil chemotaxis and adherence. Blood 58(3):658-661.
Pierce KL, Premont RT and Lefkowitz RJ (2002) Seven-transmembrane receptors. Nat Rev Mol Cell Biol 3(9):639-650.
Ptasznik A, Traynor-Kaplan A and Bokoch GM (1995) G protein-coupled chemoattractant receptors regulate Lyn tyrosine kinase.Shc adapter protein signaling complexes. J Biol Chem 270(34):19969-19973.
Quinn MT and Gauss KA (2004) Structure and regulation of the neutrophil respiratory burst oxidase: comparison with nonphagocyte oxidases. J Leukoc Biol 76(4):760-781.
Rane MJ, Carrithers SL, Arthur JM, Klein JB and McLeish KR (1997) Formyl peptide receptors are coupled to multiple mitogen-activated protein kinase cascades by distinct signal transduction pathways: role in activation of reduced nicotinamide adenine dinucleotide oxidase. J Immunol 159(10):5070-5078.
Raoof M, Zhang Q, Itagaki K and Hauser CJ (2010) Mitochondrial peptides are potent immune activators that activate human neutrophils via FPR-1. J Trauma 68(6):1328-1332; discussion 1332-1324.
Rogers KM, Dewar KM, McCubbin TD and Spence AA (1980) Preliminary experience with ICI 35 868 as an i.v. induction agent: comparison with althesin. Br J Anaesth 52(8):807-810.
Rubartelli A and Lotze MT (2007) Inside, outside, upside down: damage-associated molecular-pattern molecules (DAMPs) and redox. Trends Immunol 28(10):429-436.
Saklatvala J (2004) The p38 MAP kinase pathway as a therapeutic target in inflammatory disease. Curr Opin Pharmacol 4(4):372-377.
Salmon MD and Ahluwalia J (2011) Pharmacology of receptor operated calcium entry in human neutrophils. Int Immunopharmacol 11(2):145-148.
Sanna E, Mascia MP, Klein RL, Whiting PJ, Biggio G and Harris RA (1995) Actions of the general anesthetic propofol on recombinant human GABAA receptors: influence of receptor subunits. J Pharmacol Exp Ther 274(1):353-360.
Sasaki T, Irie-Sasaki J, Jones RG, Oliveira-dos-Santos AJ, Stanford WL, Bolon B, Wakeham A, Itie A, Bouchard D, Kozieradzki I, Joza N, Mak TW, Ohashi PS, Suzuki A and Penninger JM (2000) Function of PI3Kgamma in thymocyte development, T cell activation, and neutrophil migration. Science 287(5455):1040-1046.
Sayin MM, Ozatamer O, Tasoz R, Kilinc K and Unal N (2002) Propofol attenuates myocardial lipid peroxidation during coronary artery bypass grafting surgery. Br J Anaesth 89(2):242-246.
Schiffmann E, Corcoran BA and Wahl SM (1975) N-formylmethionyl peptides as chemoattractants for leucocytes. Proc Natl Acad Sci U S A 72(3):1059-1062.
Schilling T, Kozian A, Kretzschmar M, Huth C, Welte T, Buhling F, Hedenstierna G and Hachenberg T (2007) Effects of propofol and desflurane anaesthesia on the alveolar inflammatory response to one-lung ventilation. Br J Anaesth 99(3):368-375.
Schoneberg T, Schulz A, Biebermann H, Hermsdorf T, Rompler H and Sangkuhl K (2004) Mutant G-protein-coupled receptors as a cause of human diseases. Pharmacol Ther 104(3):173-206.
Segal AW (2005) How neutrophils kill microbes. Annu Rev Immunol 23:197-223.
Segel GB, Halterman MW and Lichtman MA (2011) The paradox of the neutrophil's role in tissue injury. J Leukoc Biol 89(3):359-372.
Selvatici R, Falzarano S, Mollica A and Spisani S (2006) Signal transduction pathways triggered by selective formylpeptide analogues in human neutrophils. Eur J Pharmacol 534(1-3):1-11.
Serezani CH, Ballinger MN, Aronoff DM and Peters-Golden M (2008) CAMP: master regulator of innate immune cell function. Am J Respir Cell Mol Biol 39(2):127-132.
Servant G, Weiner OD, Herzmark P, Balla T, Sedat JW and Bourne HR (2000) Polarization of chemoattractant receptor signaling during neutrophil chemotaxis. Science 287(5455):1037-1040.
Shiratsuchi H, Kouatli Y, Yu GX, Marsh HM and Basson MD (2009) Propofol inhibits pressure-stimulated macrophage phagocytosis via the GABAA receptor and dysregulation of p130cas phosphorylation. Am J Physiol Cell Physiol 296(6):C1400-1410.
Simchowitz L, Fischbein LC, Spilberg I and Atkinson JP (1980) Induction of a transient elevation in intracellular levels of adenosine-3',5'-cyclic monophosphate by chemotactic factors: an early event in human neutrophil activation. J Immunol 124(3):1482-1491.
Sklar LA, McNeil VM, Jesaitis AJ, Painter RG and Cochrane CG (1982) A continuous, spectroscopic analysis of the kinetics of elastase secretion by neutrophils. The dependence of secretion upon receptor occupancy. J Biol Chem 257(10):5471-5475.
Smolen JE, Korchak HM and Weissmann G (1980) Increased levels of cyclic adenosine-3',5'-monophosphate in human polymorphonuclear leukocytes after surface stimulation. J Clin Invest 65(5):1077-1085.
Takao Y, Mikawa K, Nishina K and Obara H (2005) Attenuation of acute lung injury with propofol in endotoxemia. Anesth Analg 100(3):810-816, table of contents.
Takaono M, Yogosawa T, Okawa-Takatsuji M and Aotsuka S (2002) Effects of intravenous anesthetics on interleukin (IL)-6 and IL-10 production by lipopolysaccharide-stimulated mononuclear cells from healthy volunteers. Acta Anaesthesiol Scand 46(2):176-179.
Tan AS and Berridge MV (2000) Superoxide produced by activated neutrophils efficiently reduces the tetrazolium salt, WST-1 to produce a soluble formazan: a simple colorimetric assay for measuring respiratory burst activation and for screening anti-inflammatory agents. J Immunol Methods 238(1-2):59-68.
Taniguchi T, Kanakura H and Yamamoto K (2002) Effects of posttreatment with propofol on mortality and cytokine responses to endotoxin-induced shock in rats. Crit Care Med 30(4):904-907.
Taniguchi T, Yamamoto K, Ohmoto N, Ohta K and Kobayashi T (2000) Effects of propofol on hemodynamic and inflammatory responses to endotoxemia in rats. Crit Care Med 28(4):1101-1106.
Tintinger GR, Steel HC, Theron AJ and Anderson R (2009) Pharmacological control of neutrophil-mediated inflammation: strategies targeting calcium handling by activated polymorphonuclear leukocytes. Drug Des Devel Ther 2:95-104.
Tsuchiya S, Yamabe M, Yamaguchi Y, Kobayashi Y, Konno T and Tada K (1980) Establishment and characterization of a human acute monocytic leukemia cell line (THP-1). Int J Cancer 26(2):171-176.
Vanlersberghe C and Camu F (2008) Propofol. Handb Exp Pharmacol(182):227-252.
Vlahos CJ, Matter WF, Brown RF, Traynor-Kaplan AE, Heyworth PG, Prossnitz ER, Ye RD, Marder P, Schelm JA, Rothfuss KJ and et al. (1995) Investigation of neutrophil signal transduction using a specific inhibitor of phosphatidylinositol 3-kinase. J Immunol 154(5):2413-2422.
Wang H, Xue Z, Wang Q, Feng X and Shen Z (2008) Propofol protects hepatic L02 cells from hydrogen peroxide-induced apoptosis via activation of extracellular signal-regulated kinases pathway. Anesth Analg 107(2):534-540.
Wheeler DW, Thompson AJ, Corletto F, Reckless J, Loke JC, Lapaque N, Grant AJ, Mastroeni P, Grainger DJ, Padgett CL, O'Brien JA, Miller NG, Trowsdale J, Lummis SC, Menon DK and Beech JS (2011) Anaesthetic impairment of immune function is mediated via GABA(A) receptors. PLoS One 6(2):e17152.
White PF (2008) Propofol: its role in changing the practice of anesthesia. Anesthesiology 109(6):1132-1136.
Ye RD, Boulay F, Wang JM, Dahlgren C, Gerard C, Parmentier M, Serhan CN and Murphy PM (2009) International Union of Basic and Clinical Pharmacology. LXXIII. Nomenclature for the formyl peptide receptor (FPR) family. Pharmacol Rev 61(2):119-161.
Yellon DM and Hausenloy DJ (2007) Myocardial reperfusion injury. N Engl J Med 357(11):1121-1135.
Yu HP (2011) Role of anesthetic agents on cardiac and immune systems. Shock 36(6):532-541.
Yu HP, Hsieh PW, Chang YJ, Chung PJ, Kuo LM and Hwang TL (2009) DSM-RX78, a new phosphodiesterase inhibitor, suppresses superoxide anion production in activated human neutrophils and attenuates hemorrhagic shock-induced lung injury in rats. Biochem Pharmacol 78(8):983-992.
Yu HP, Hsieh PW, Chang YJ, Chung PJ, Kuo LM and Hwang TL (2011) 2-(2-Fluorobenzamido)benzoate ethyl ester (EFB-1) inhibits superoxide production by human neutrophils and attenuates hemorrhagic shock-induced organ dysfunction in rats. Free Radic Biol Med 50(12):1737-1748.
Yu HP, Lui PW, Hwang TL, Yen CH and Lau YT (2006) Propofol improves endothelial dysfunction and attenuates vascular superoxide production in septic rats. Crit Care Med 34(2):453-460.
Zarubin T and Han J (2005) Activation and signaling of the p38 MAP kinase pathway. Cell Res 15(1):11-18.
Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, Brohi K, Itagaki K and Hauser CJ (2010) Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464(7285):104-107.
Zhang SH, Wang SY and Yao SL (2004) Antioxidative effect of propofol during cardiopulmonary bypass in adults. Acta Pharmacol Sin 25(3):334-340.