エンドトキシン誘発の全身性炎症に対して1日齢マウスの脳が行う初期の免疫応答
早産児に全身性炎症が生じると神経学的後遺症が発症するが，全身性炎症が脳に炎症環境をもたらす仕組みには謎が多い。ここでは新生仔マウスにEscherichia coli O55 : B5由来のエンドトキシンであるlipopolysaccharide （LPS）を腹腔内投与し，頭蓋内のどの部位のマクロファージ（Mϕ）／ミクログリアがinterleukin （IL）-1βを産生するかを明らかにした。1日齢マウスにLPSもしくは生理食塩水を腹腔内投与し，1または4時間後に頭部を固定し凍結切片を作製した。F4/80をMϕ／ミクログリアの，IL-1βを炎症応答のマーカーとして二重免疫蛍光染色を行い，脈絡叢，...
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| Published in | 杏林医学会雑誌 Vol. 55; no. 2; pp. 49 - 57 |
|---|---|
| Main Authors | , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
杏林医学会
02.07.2024
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0368-5829 1349-886X |
| DOI | 10.11434/kyorinmed.55.49 |
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| Abstract | 早産児に全身性炎症が生じると神経学的後遺症が発症するが，全身性炎症が脳に炎症環境をもたらす仕組みには謎が多い。ここでは新生仔マウスにEscherichia coli O55 : B5由来のエンドトキシンであるlipopolysaccharide （LPS）を腹腔内投与し，頭蓋内のどの部位のマクロファージ（Mϕ）／ミクログリアがinterleukin （IL）-1βを産生するかを明らかにした。1日齢マウスにLPSもしくは生理食塩水を腹腔内投与し，1または4時間後に頭部を固定し凍結切片を作製した。F4/80をMϕ／ミクログリアの，IL-1βを炎症応答のマーカーとして二重免疫蛍光染色を行い，脈絡叢，頭部間葉，脳実質にてF4/80陽性細胞のIL-1β陽性率を求めた。IL-1β陽性率はLPS投与4時間後の脈絡叢で64.3％，頭部間葉で6.5％と上昇し，脳実質では上昇しなかった。従って，1日齢マウスでは全身性炎症に応答して脈絡叢・頭部間葉のMϕが免疫反応を開始すること，脳実質のミクログリアは初期応答を行わないことが分かった。 |
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| AbstractList | 早産児に全身性炎症が生じると神経学的後遺症が発症するが，全身性炎症が脳に炎症環境をもたらす仕組みには謎が多い。ここでは新生仔マウスにEscherichia coli O55 : B5由来のエンドトキシンであるlipopolysaccharide （LPS）を腹腔内投与し，頭蓋内のどの部位のマクロファージ（Mϕ）／ミクログリアがinterleukin （IL）-1βを産生するかを明らかにした。1日齢マウスにLPSもしくは生理食塩水を腹腔内投与し，1または4時間後に頭部を固定し凍結切片を作製した。F4/80をMϕ／ミクログリアの，IL-1βを炎症応答のマーカーとして二重免疫蛍光染色を行い，脈絡叢，頭部間葉，脳実質にてF4/80陽性細胞のIL-1β陽性率を求めた。IL-1β陽性率はLPS投与4時間後の脈絡叢で64.3％，頭部間葉で6.5％と上昇し，脳実質では上昇しなかった。従って，1日齢マウスでは全身性炎症に応答して脈絡叢・頭部間葉のMϕが免疫反応を開始すること，脳実質のミクログリアは初期応答を行わないことが分かった。 |
| Author | 島田, 厚良 摂津, 黎 樽井, 武彦 小原, 映 |
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Lancet Psychiatry. 2015; 2: 258-70. 10) Volpe JJ. Dysmaturation of Premature Brain: Importance, Cellular Mechanisms, and Potential Interventions. Pediatr Neurol. 2019; 95: 42-66. 30) Saunders NR, Liddelow SA, Dziegielewska KM. Barrier mechanisms in the developing brain. Front Pharmacol. 2012; 3: 46. 21) Li Q, Barres BA. Microglia and macrophages in brain homeostasis and disease. Nat Rev Immunol. 2018; 18: 225-242. |
| References_xml | – reference: 2) Erickson MA, Banks WA. Neuroimmune Axes of the Blood-Brain Barriers and Blood-Brain Interfaces: Bases for Physiological Regulation, Disease States, and Pharmacological Interventions. Pharmacol Rev. 2018; 70: 278-314. – reference: 19) Alliot F, Godin I, Pessac B. Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Brain Res Dev Brain Res. 1999; 117: 145-52. – reference: 21) Li Q, Barres BA. Microglia and macrophages in brain homeostasis and disease. Nat Rev Immunol. 2018; 18: 225-242. – reference: 12) Laverty C, Surtees A, O'Sullivan R, Sutherland D, Jones C, Richards C. The prevalence and profile of autism in individuals born preterm: a systematic review and meta-analysis. J Neurodev Disord. 2021; 13: 41. – reference: 8) van der Slikke EC, Beumeler LFE, Holmqvist M, Linder A, Mankowski RT, Bouma HR. Understanding Post-Sepsis Syndrome: How Can Clinicians Help? Infect Drug Resist. 2023; 16: 6493-6511. – reference: 30) Saunders NR, Liddelow SA, Dziegielewska KM. Barrier mechanisms in the developing brain. Front Pharmacol. 2012; 3: 46. – reference: 5) Amor S, Peferoen LA, Vogel DY, Breur M, van der Valk P, Baker D, van Noort JM. Inflammation in neurodegenerative diseases--an update. Immunology. 2014; 142: 151-66. – reference: 1) Dantzer R. Neuroimmune Interactions: From the Brain to the Immune System and Vice Versa. Physiol Rev. 2018; 98: 477-504. – reference: 28) Ek CJ, Dziegielewska KM, Habgood MD, Saunders NR. Barriers in the developing brain and Neurotoxicology. Neurotoxicology. 2012; 33: 586-604. – reference: 25) Strazielle N, Ghersi-Egea JF. Choroid plexus in the central nervous system: biology and physiopathology. J Neuropathol Exp Neurol. 2000; 59: 561-74. – reference: 23) Erickson MA, Banks WA. Cytokine and chemokine responses in serum and brain after single and repeated injections of lipopolysaccharide: multiplex quantification with path analysis. Brain Behav Immun. 2011; 25: 1637-48. – reference: 4) Khandaker GM, Cousins L, Deakin J, Lennox BR, Yolken R, Jones PB. Inflammation and immunity in schizophrenia: implications for pathophysiology and treatment. Lancet Psychiatry. 2015; 2: 258-70. – reference: 16) Hasegawa-Ishii S, Inaba M, Shimada A. Widespread time-dependent changes in tissue cytokine concentrations in brain regions during the acute phase of endotoxemia in mice. Neurotoxicology. 2020; 76: 67-74. – reference: 17) Shimada A, Hasegawa-Ishii S. Increased cytokine expression in the choroid plexus stroma and epithelium in response to endotoxin-induced systemic inflammation in mice. Toxicol Rep. 2021; 8: 520-528. – reference: 13) Shimada A, Murata M, Obara A. Brain immunological responses to endotoxin-induced systemic inflammation in adult mice. J. Kyorin Med. Soc. 2023; 54: 49-57. – reference: 27) Fedorko ME, Hirsch JG, Fried B. Studies on transport of macromolecules and small particles across mesothelial cells of the mouse omentum. II. Kinetic features and metabolic requirements. Exp Cell Res. 1971; 69: 313-23. – reference: 9) Liu L, Oza S, Hogan D, Chu Y, Perin J, Zhu J, Lawn JE, Cousens S, Mathers C, Black RE. Global, regional, and national causes of under-5 mortality in 2000-15: an updated systematic analysis with implications for the Sustainable Development Goals. Lancet. 2016; 388: 3027-3035. – reference: 20) Ginhoux F, Lim S, Hoeffel G, Low D, Huber T. Origin and differentiation of microglia. Front Cell Neurosci. 2013; 7: 45. – reference: 7) Gofton TE, Young GB. Sepsis-associated encephalopathy. Nat Rev Neurol. 2012; 8: 557-66. – reference: 22) Banks WA, Robinson SM. Minimal penetration of lipopolysaccharide across the murine blood-brain barrier. Brain Behav Immun. 2010; 24: 102-9. – reference: 26) Shoyaib AA, Archie SR, Karamyan VT. Intraperitoneal Route of Drug Administration: Should it Be Usedin Experimental Animal Studies? Pharm Res. 2020; 37: 12. – reference: 11) Strunk T, Inder T, Wang X, Burgner D, Mallard C, Levy O. Infection-induced inflammation and cerebral injury in preterm infants. Lancet Infect Dis. 2014; 14: 751-762. – reference: 3) Troubat R, Barone P, Leman S, Desmidt T, Cressant A, Atanasova B, Brizard B, El Hage W, Surget A, Belzung C, Camus V. Neuroinflammation and depression: A review. Eur J Neurosci. 2021; 53: 151-171. – reference: 14) Dasgupta K, Jeong J. Developmental biology of the meninges. Genesis. 2019; 57: e23288. – reference: 18) Shimada A, Murata M, Aoyagi S, Asano H, Obara A, Hasegawa-Ishii S. Delayed microglial activation associated with the resolution of neuroinflammation in a mouse model of sublethal endotoxemia-induced systemic inflammation. Toxicol Rep. 2022; 9: 1380-1390. – reference: 6) Kelley KW, Peng YP, Liu Q, Chang HC, Spencer SJ, Hutchinson MR, Shimada A. Psychoneuroimmunology goes East: Development of the PNIRSChina affiliate and its expansion into PNIRSAsia-Pacific. Brain Behav Immun. 2020; 88: 75-87. – reference: 10) Volpe JJ. Dysmaturation of Premature Brain: Importance, Cellular Mechanisms, and Potential Interventions. Pediatr Neurol. 2019; 95: 42-66. – reference: 24) Mastorakos P, McGavern D. The anatomy and immunology of vasculature in the central nervous system. Sci Immunol. 2019; 4: eaav0492. – reference: 15) Hasegawa-Ishii S, Inaba M, Umegaki H, Unno K, Wakabayashi K, Shimada A. Endotoxemia-induced cytokine-mediated responses of hippocampal astrocytes transmitted by cells of the brain-immune interface. Sci Rep. 2016; 6: 25457. – reference: 29) Daneman R, Zhou L, Kebede AA, Barres BA. Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature. 2010; 468: 562-6. |
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| Snippet | 早産児に全身性炎症が生じると神経学的後遺症が発症するが，全身性炎症が脳に炎症環境をもたらす仕組みには謎が多い。ここでは新生仔マウスにEscherichia coli O55 : B5由来のエンドトキシンであるlipopolysaccharide... |
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| SubjectTerms | エンドトキシン マクロファージ ミクログリア 脈絡叢 髄膜 |
| Title | エンドトキシン誘発の全身性炎症に対して1日齢マウスの脳が行う初期の免疫応答 |
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