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Pulmonary Fibrosis caused by Asbestos Fibers in the Respiratory Airway
Biomed Sci Letters 2021;27:111-120
Published online September 30, 2021;  https://doi.org/10.15616/BSL.2021.27.3.111
© 2021 The Korean Society For Biomedical Laboratory Sciences.

Ji-Woo Jung* and Eung-Sam Kim†,* *

Department of Biological Sciences, Chonnam National University, Gwangju 61186, Korea
Correspondence to: Eung-Sam Kim. Department of Biological Sciences, Research Center of Ecomimetics, Research Center of Next-Generation Sensors, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 61186, Korea.
Tel: +82-62-530-3416, Fax: +82-62-530-3409, e-mail: eungsam.kim@chonnam.ac.kr
*Undergraduate student, **Professor.
Received August 18, 2021; Revised September 17, 2021; Accepted September 24, 2021.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract
Asbestos products had been widely used until 2007 in Korea since the 1930s. A total ban on their production and applications has been imposed because of the toxic effect of asbestos fibers on the human health. The inhaled asbestos fibers increase reactive oxygen species and inflammatory reactions in the respiratory airway including the alveolar sac, resulting in DNA damages and secretion of several inflammatory cytokines or chemokines. These paracrine communications promote the proliferation of fibroblasts and the synthesis of collagen fibers, thereby depositing them into the extracellular matrix at the interstitial space of alveoli. The fibrotic tissue hindered the gas exchange in the alveolus. This reviews describes not only the cytotoxic effects of asbestos fibers with different physical or chemical characteristics but also the interaction of cells that make up the respiratory airway to understand the molecular or cellular mechanisms of asbestos fiber-induced toxicity. In addition, we propose a pulmonary toxicity research technique based on the mini-lung that can mimic human respiratory system as an alternative to overcome the limitations of the conventional risk assessment of asbestos fibers.
Keywords : Asbestos fiber, Respiratory airway, Pulmonary inflammation, Pulmonary fibrosis, Mini-lung
꽌 濡

꽍硫(asbestos) 솕궛솢룞뿉 쓽빐 諛쒖깮븳 솕꽦븫쓽 씪醫낆쑝濡 洹쒖궛뿼 꽟쑀(silicate fiber)쓽 떎諛쒖씠 紐⑥뿬 삎꽦맂 愿묐Ъ씠떎. 꽍硫 湲곕컲쓽 젣뭹 媛寃⑹씠 졃븯怨 궡援ъ꽦씠 슦닔븷 肉 븘땲씪 떒뿴 諛 蹂댁삩 湲곕뒫씠 쎇뼱굹 怨쇨굅 援궡뿉꽌 嫄댁텞옱, 留덉같옱, 諛⑹쭅옱 삎깭濡 떎뼇븯寃 궗슜릺뿀떎. 援궡뿉꽌뒗 1930뀈뿉 꽍硫 愿묒궛씠 媛쒕컻릺湲 떆옉븯硫댁꽌 蹂멸꺽쟻쑝濡 꽍硫 젣뭹씠 깮궛릺湲 떆옉뻽怨, 2006뀈源뚯 꽍硫 젣뭹쓽 닔엯웾룄 뒛뿀뜕 留뚰겮 吏궃 100뿬뀈 룞븞 꽍硫 궗슜웾 袁몄엳 利앷빐솕떎. 1970뀈源뚯 媛삦쓽 吏遺 뒳젅씠듃뿉 二쇰줈 궗슜릺뜕 꽍硫댁 1990뀈뿉 뱾뼱꽌硫댁꽌 蹂댁삩떒뿴옱, 泥쒖젙뙋 벑 떎뼇븳 嫄댁텞옄옱濡 솢슜릺硫댁꽌 궗슜웾쓽 利앷肉먮쭔 븘땲씪 愿묐쾾쐞븯寃 씠슜릺뿀떎(Choi et al., 1988). 洹몃윭굹 씤泥댁뿉 븳 꽍硫댁쓽 쐞빐꽦씠 蹂닿퀬릺湲 떆옉븯硫댁꽌 1987뀈 꽭怨꾨낫嫄닿린援(WHO)뒗 꽍硫댁쓣 1湲 諛쒖븫 臾쇱쭏(carcinogen)濡 吏젙븯떎. 씠뿉 뵲씪 떎닔쓽 援媛뱾씠 꽍硫 씠슜쓣 쟾硫 湲덉븯뒗 議곗튂瑜 痍⑦븯湲 떆옉뻽怨, 슦由щ굹씪뿉꽌룄 2009뀈 꽍硫닿낵 꽍硫 젣뭹쓽 젣議, 궗슜, 쑀넻 諛 닔엯씠 쟾硫 湲덉 릺뿀떎(Kim, 2009).

援궡뿉꽌 蹂닿퀬맂 꽍硫닿젴 씤泥 뵾빐 궗濡瑜 궡렣蹂대㈃, 援궡 꽍硫대갑吏곴났옣 洹쇰줈옄뿉寃뚯꽌 諛쒕퀝븳 븙꽦 以묓뵾醫 (malignant mesothelioma)씠 꽍硫닿젴 궛뾽옱빐濡 1993뀈뿉 泥섏쓬쑝濡 씤젙맂 썑, 룞씪븳 궗뾽옣뿉꽌 異붽쟻쑝濡 븙꽦 以묓뵾醫 5嫄, 꽍硫댄룓(asbestosis) 7嫄댁씠 諛쒖깮븳 寃껋쑝濡 議곗궗릺뿀떎(Gang, 2009). 씠썑 理쒓렐源뚯 꽍硫닿낵 愿젴맂 援궡 뵾빐 궗濡뒗 袁몄엳 利앷븯떎(Table 1). 10뿬뀈 쟾源뚯 꽍硫 젣뭹쓽 궗슜씠 吏냽릺뼱 솕뿀怨 꽍硫 끂異쒖뿉 뵲瑜 吏곸젒쟻씤 吏덈퀝 諛 빀蹂묒쬆씠 30~40뀈 씠썑뿉 굹굹뒗 젏쓣 怨좊젮븯硫 2030뀈源뚯룄 꽍硫 뵾빐 궗濡뱾 袁몄엳 蹂닿퀬맆 寃껋쑝濡 쟾留앸릺怨 엳떎(Ko et al., 2020). 2009뀈 쟾硫 湲덉 議곗튂媛 궡젮吏 씠썑뿉 湲곗〈뿉 깮궛릺뿀뜕 꽍硫 젣뭹 룓湲곕릺뿀怨 꽍硫 嫄댁텞옄옱媛 궗슜맂 嫄대Ъ 빐泥 怨쇱젙뿉꽌 쇅遺濡 꽍硫댁씠 쑀異쒕릺吏 븡룄濡 뾼寃⑺븳 젅李⑥뿉 뵲씪 빐泥대릺怨 엳떎. 2021뀈 쁽옱 솚寃쎈 꽍硫닿由ъ쥌빀젙蹂대쭩쓽 넻怨꾩옄猷뚯뿉 쓽븯硫 援궡뿉 22,079嫄댁쓽 꽍硫닿굔異뺣Ъ씠 뿬쟾엳 議댁옱븯硫 洹 以묒뿉 怨듦났嫄댁텞臾쇱씠굹 뼱由곗씠吏묐룄 긽떦닔 룷븿릺뼱 엳뼱 꽍硫 끂異쒖뿉 쓽븳 뵾빐 쐞뿕 쁽옱 吏꾪뻾삎씤 떎젙씠떎.

Asbestos-related pulmonary diseases in Korea from 2014 to 2019 (source: Ko et al., 2020)

(unit: person)

Year Asbestosis Malignant mesothelioma Lung cancer Diffuse pleural thickening Total
2014 162 42 21 2 227
2015 199 41 48 - 288
2016 294 45 75 2 416
2017 313 62 74 - 449
2018 395 59 68 - 522
2019 526 47 73 - 646


꽍硫댁뿉 쓽븳 떊泥댁쟻 뵾빐뒗 利됯컖쟻쑝濡 諛쒖깮븯吏 븡湲 븣臾몄뿉 꽍硫댁쓽 듅꽦怨 꽍硫댁뿉 끂異쒕맂 샇씉怨꾩쓽 蹂솕瑜 옒 씠빐븯吏 紐삵븳떎硫 꽍硫댁쓽 쐞빐꽦쓣 媛꾧낵븯湲 돺떎. 꽍硫댁 媛뒓떎 꽍硫댁꽟쑀(asbestos fiber)쓽 떎諛쒕줈 援ъ꽦맂 愿묐Ъ씠湲 븣臾몄뿉 쇅遺 슂씤뿉 쓽빐 꽟쑀 삎깭濡 돺寃 遺꾨━맆 닔 엳떎. 꽍硫댁꽟쑀뒗 0.05~10 μm 湲몄씠쓽 誘몄꽭엯옄 삎깭濡 怨듦린 以묒뿉 遺쑀븷 닔 엳떎. 궗엺쓽 샇씉 怨쇱젙쓣 넻빐 씉엯맂 꽍硫댁꽟쑀뒗 쟾룄湲곕룄(conducting airway)瑜 援ъ꽦븯뒗 湲곌, 湲곌吏, 꽭湲곌吏瑜 닚李⑥쟻쑝濡 넻怨쇳븯뿬 샇씉湲곗쓽 留먮떒 遺遺꾩씤 샇씉湲곕룄(respiratory airway)源뚯 룄떖븷 닔 엳떎. 꽍硫댁꽟쑀媛 샇씉湲곕룄뿉 룄떖븯뿬 異뺤쟻릺硫 샇씉湲곕룄瑜 援ъ꽦븯뒗 긽뵾꽭룷(epithelial cell) 떇꽭룷(macrophage)뿉꽌 솢꽦궛냼醫(reactive oxygen species)쓣 諛쒖깮떆궎嫄곕굹 議곗쭅뿉 臾쇰━쟻 넀긽쓣 씪쑝궓떎. 꽍硫댁꽟쑀 끂異 珥덇린뿉 샇씉湲곕룄뿉 쑀諛쒕맂 뿼利앸컲쓳 씠썑 꽍硫댁꽟쑀媛 떇꽭룷뿉 쓽빐 젣嫄곕릺吏 븡쓣 寃쎌슦 留뚯꽦쟻 뿼利앸컲쓳쑝濡 吏꾪뻾맂떎(Macnab and Harington, 1967; Rosenthal et al., 1999). 씠 븣 遺꾨퉬릺뒗 궗씠넗移댁씤(cytokine)뱾 샇씉湲곕룄뿉 議댁옱븯뒗 꽟쑀븘꽭룷(fibroblast)濡쒕꽣 肄쒕씪寃(collagen) 빀꽦쓣 珥됱쭊떆耳 꽭룷쇅湲곗쭏(extracellular matrix, ECM)쓣 몢猿띻쾶 留뚮뱺떎. 洹 寃곌낵 샇씉湲곕룄뿉꽌 湲곗껜援먰솚(gas exchange)씠 옒 씪뼱굹吏 븡뒗 긽깭씤 誘몃쭔꽦 쓨留됰퉬썑(diffuse pleural thickening)媛 뿬윭 룓룷뿉꽌 諛쒓껄릺뒗 꽍硫댄룓濡 븙솕맆 닔 엳떎. 샇씉湲곕룄 媛슫뜲 룓룷(alveolar sac) 룓룷愿(alveolar duct) 湲곗껜援먰솚(gas exchange)씠 媛옣 솢諛쒗븯寃 씪뼱굹뒗 遺쐞씠湲 븣臾몄뿉 꽍硫댁꽟쑀濡 씤븳 뿼利앸컲쓳 諛 꽟쑀솕뒗 뼢썑 移섎챸쟻씤 寃곌낵瑜 珥덈옒븷 닔 엳떎.

쟾룄湲곕룄쓽 꽟紐⑥ 젏븸씠 꽍硫댁꽟쑀媛 샇씉湲곕룄源뚯 룄떖븯뒗 寃껋쓣 뼲젣븯뒗 뿭븷쓣 븯湲 븣臾몄뿉 꽍硫댁꽟쑀媛 샇씉湲곕룄뿉 룄떖븷 솗瑜좎 긽쟻쑝濡 궙 렪씠떎. 湲곗〈쓽 뿬윭 뿰援щ뱾 샇씉湲곕룄 씠쟾 遺쐞뿉 異뺤쟻맂 꽍硫댁꽟쑀뿉 븳 뵾빐 궗濡뱾뿉 珥덉젏쓣 留욎텛뿀떎. 븯吏留 꽟紐⑥ 젏븸留뚯쑝濡쒕뒗 꽍硫댁꽟쑀媛 샇씉湲곕룄뿉 룄떖븯뒗 寃껋쓣 셿踰쏀븯寃 留됱쓣 닔 뾾怨 쟾룄湲곕룄뿉 異뺤쟻맂 꽍硫댁꽟쑀媛 뙆렪솕릺뼱 샇씉湲곕룄源뚯 룄떖븷 닔 엳뼱 씠뿉 븳 紐낇솗븳 씠빐媛 븘슂븳 떎젙씠떎. 씠뿉 蹂 珥앹꽕 꽍硫댁꽟쑀媛 湲곗껜援먰솚씠 솢諛쒗븯寃 씪뼱굹뒗 뻼 議곗쭅꽭룷痢듭쑝濡 援ъ꽦맂 샇씉湲곕룄뿉 빞湲고븯뒗 쐞빐꽦 湲곗쟾쓣 遺꾩옄 • 꽭룷 깮臾쇳븰쟻 愿젏뿉꽌 젙由ы븯怨좎옄 븳떎. 꽍硫댁꽟쑀뿉 쓽빐 샇씉湲곕룄뿉꽌 씪뼱굹뒗 룓 꽟쑀솕(pulmonary fibrosis) 怨쇱젙쓣 룓룷 떇꽭룷(alveolar macrophage)쓽 愿뿬 뿬遺뿉 뵲瑜 몢 媛吏 怨쇱젙쑝濡 굹늻뼱 湲곗쟾쓣 꽕紐낇븷 寃껋씠떎. 씠瑜 넻빐, 꽍硫댁꽟쑀쓽 쐞빐꽦怨 샇씉湲곕룄쓽 룓 꽟쑀솕利앹쓣 蹂대떎 紐낇솗븯寃 씠빐븯뒗뜲 룄쓣 二쇨퀬옄 븳떎. 삉븳 吏湲덇퉴吏 洹 以묒슂꽦씠 媛꾧낵릺뼱솕뜕 룓 議곗쭅쓽 湲곌퀎쟻 옄洹 솚寃쎌뿉 븳 옱怨좎쓽 븘슂꽦怨 理쒖떊 룓 議곗쭅 紐⑥궗 떎뿕 紐⑤뜽쓣 냼媛쒗븿쑝濡쒖뜥 꽍硫닿젴 룓 吏덊솚쓽 移섎즺 옱솢 諛⑸쾿 媛쒕컻뿉 깉濡쒖슫 떆媛곸쓣 젣떆븯怨좎옄 븳떎.

蹂 濡

꽍硫댁꽟쑀쓽 醫낅쪟 臾쇰━솕븰쟻 꽦吏

꽍硫댁 愿묐Ъ븰쟻 遺꾨쪟뿉 뵲씪 궗臾몄꽍(serpentine) 怨꾩뿴怨 媛곸꽟꽍(amphibolite) 怨꾩뿴濡 굹닃 닔 엳떎. 몴쟻쑝濡 궗臾몄꽍 怨꾩뿴뿉뒗 諛깆꽍硫(chrysotile)씠 엳怨, 媛곸꽟꽍 怨꾩뿴뿉뒗 泥꽍硫(crocidolite)怨 媛덉꽍硫(amosite)씠 엳떎(Table 2). 긽뾽쟻쑝濡 궗슜릺뒗 꽍硫댁쓽 95%뒗 諛깆꽍硫댁씠硫, 泥꽍硫댁씠 씪遺 궗슜릺吏留 굹癒몄 꽍硫댁 긽뭹꽦씠 궙븘 嫄곗쓽 궗슜릺吏 븡뒗떎. 諛깆꽍硫댁 吏덈웾떦 꽟쑀떎諛 닔媛 留롪퀬(쟾泥 몴硫댁쟻씠 겕떎뒗 寃껋쓣 쓽誘명븿) 꽟쑀援ъ“쓽 諛곗뿴씠 遺덇퇋移숈쟻씠떎(Solbes and Harper, 2018). 씠뿉 鍮꾪빐 媛곸꽟꽍 怨꾩뿴쓽 꽟쑀뒗 怨㏐퀬 겕湲곌 洹좎씪븯떎.

Comparison of serpentine and amphibole asbestos

Serpentine Amphibole
Chemical formula Chrysotile [Mg3(Si2O5)(OH)4] Crocidolite [Na2Fe2(FeMg)3Si8O22(OH)2]
Amosite [(Fe,Mg)7Si8O22(OH)2]
Chemical structure Extended sheet Double chain

(Image source: Hanley et al., 2001)

(Image source: Hanley et al., 2001)
Representative SEM image
(Image source: Kim et al., 2010)

(Image source: Toyokuni, 2009)
Fiber shape Curly Straight
Surface area per mass Large Small
Cytotoxicity Less toxic Toxic
Commercial uses until 2007 in Korea Most frequently used Rarely used


꽍硫댁쓣 援ъ꽦븯뒗 꽟쑀瑜 꽍硫댁꽟쑀씪怨 遺瑜몃떎. 꽟쑀瑜 援ъ꽦븯뒗 떒쐞泥대뒗 洹쒖궛뿼(silicate, SiO44-)씠硫 꽍硫댁꽟쑀뒗 Si-O-Si 寃고빀쑝濡 뿰寃곕맂 以묓빀泥댁씠떎. 媛곸꽟꽍 怨꾩뿴 꽍硫댁 洹쒖궛뿼 以묓빀泥 궗뒳 몢 媛떏씠 뿰寃곕맂 援ъ“씠硫, 궗臾몄꽍 怨꾩뿴 꽍硫댁 洹쒖궛뿼쓽 닔룊쟻 뿰寃곗씠 솗옣맂 삎깭씠吏留, 썝옄媛꾩쓽 寃고빀 쐞移섍 議곌툑뵫 뾿媛덈젮 엳湲 븣臾몄뿉 뮘由 룊硫닿뎄議곕 媛吏꾨떎. 쓬쟾븯瑜 씈뒗 洹쒖궛뿼 꽟쑀쓽 몴硫댁뿉뒗 泥(Fe3+) 샊 留덇렇꽕뒛(Mg2+)怨 媛숈 湲덉냽 씠삩씠 遺숈쓣 닔 엳떎. 洹 以묒뿉꽌 泥 씠삩怨 洹쒖궛뿼 꽟쑀濡 援ъ꽦맂 꽍硫댁꽟쑀媛 泥대궡 쑀엯씠 릺뼱 怨쇰룄븳 솢꽦궛냼醫낆씠 留뚮뱾뼱졇 꽭룷룆꽦씠 굹굹寃 맂떎.

궛냼 솚寃쎌뿉꽌 Fe3+뒗 넂 썝옄媛 긽깭瑜 쑀吏븯湲 븣臾몄뿉 洹 諛섏쓳꽦씠 겕떎. 뵲씪꽌 Fe3+뒗 꽍硫댁쓽 洹쒖궛吏 몴硫닿낵 돺寃 寃고빀븯뒗뜲 씠뒗 留덉튂 Fe3+媛 솚썝릺뒗 寃껉낵 쑀궗븳 슚怨쇰 굹궦떎(Ghio et al., 1998). 洹몃━怨 씠 몴硫댁쓽 Fe3+媛 떎젣濡 솚썝릺硫, Haber-Weiss 諛섏쓳怨 Fenton 諛섏쓳쓣 씪쑝궓떎(Fig. 1). 洹 寃곌낵 룓룷 꽭룷 諛 럹룷 硫댁뿭꽭룷뿉꽌 ·O2-굹 ·OH 媛숈 솢꽦궛냼醫낆씠 留뚮뱾뼱吏꾨떎. 씠 솢꽦궛냼醫낆 꽭룷 솚寃쎌뿉꽌 iNOS (inducible nitric oxide synthase) 諛섏쓳븯뿬 솢꽦吏덉냼醫(reactive nitrogen species)쓣 留뚮뱾湲곕룄 븳떎(Sun et al., 2010). 솢꽦궛냼醫낃낵 솢꽦吏덉냼醫낆 DNA, 떒諛깆쭏, 吏吏덉뿉 臾댁옉쐞쟻 넀긽쓣 씪쑝궗 닔 엳떎(Fontecave et al., 1990). 씠윭븳 씪뵒移 諛섏쓳 醫낃껐 씠쟾源뚯 怨꾩냽 二쇰쑝濡 쟾뙆릺硫 諛섏쓳씠 吏꾪뻾릺뒗 듅꽦씠 엳쑝硫 꽭룷 꽍硫댁꽟쑀媛 젒珥됲븯뒗 硫댁쟻뿉 鍮꾨븳떎. 媛곸꽟꽍 怨꾩뿴 꽍硫댁꽟쑀蹂대떎 吏덈웾떦 몴硫댁쟻씠 겙 궗臾몄꽍 怨꾩뿴 꽍硫댁꽟쑀뒗 솢꽦궛냼醫 諛쒖깮 뒫젰씠 겕떎뒗 寃껋씠 蹂닿퀬릺뿀떎(Ghio et al., 1998). 꽍硫댁꽟쑀쓽 吏덈웾떦 몴硫댁쟻씠 겕硫 꽭룷 젒珥됰㈃룄 而ㅼ硫댁꽌 솢꽦궛냼醫낆쓣 諛쒖깮떆궗 솗瑜좎씠 넂븘吏 닔 엳吏留 꽍硫댁꽟쑀쓽 꽭룷룆꽦뿉 엳뼱 솢꽦궛냼醫낆쓽 諛쒖깮 씠쇅뿉 떎瑜 슂씤뱾씠 愿뿬븳떎.

Fig. 1. Scheme of the biochemical process for generation of reactive oxygen or nitrogen species in alveolar or inflammatory cells exposed to asbestos fibers. (A) Harber-Weiss reaction. (B) Fenton reaction (Abbreviations: iNOS, inducible nitric oxide synthase).

룓쓽 援ъ“ 샇씉湲곕룄瑜 援ъ꽦븯뒗 꽭룷뱾

씤媛꾩쓽 룓뒗 4二쇱감쓽 깭븘뿉꽌 룓븘(lung bud)뿉꽌 遺꾩(branching)릺뼱 1꽭 二쇨린愿吏瑜 삎꽦븳떎(Kwan et al., 2010). 씠썑 23꽭源뚯 遺꾩媛 씪뼱굹 셿쟾븳 룓 援ъ“瑜 삎꽦븯뒗뜲 湲곕룄쓽 遺꾩맂 꽭뿉 뵲씪 빐遺븰쟻 遺꾨쪟媛 媛뒫븯떎. 遺꾩媛 씪뼱궃 遺꾧린젏 湲곕룄遺꾧린젏(airway bifurcation), 5~16꽭瑜 留먮떒꽭湲곌吏(terminal bronchiole), 17~19꽭瑜 샇씉꽭湲곌吏(respiratory bronchiole), 20~22꽭瑜 룓룷愿(alveolar duct), 23꽭瑜 룓룷궘(alveolar sac)씠씪怨 紐낅챸븳떎. 留먮떒꽭湲곌吏源뚯 湲곗껜援먰솚뿉 愿뿬븯吏 븡뒗 遺쐞뒗 쟾룄湲곕룄씠硫, 17꽭 븘옒쓽 湲곌吏뒗 湲곗껜援먰솚뿉 吏곸젒 愿뿬븯湲 븣臾몄뿉 샇씉湲곕룄濡 遺꾨쪟븳떎(Fig. 2).

Fig. 2. Pulmonary fibrosis associated with the exposure time or amount of asbestos fibers. The normal, inflammatory, and fibrotic alveoli are colored in white, yellow, and red, respectively. (A) Early phase of alveolar fibrosis by asbestos fibers. (B) Pulmonary fibrosis by sustained exposure to asbestos fibers.

긽쟻쑝濡 議곗쭅꽭룷痢듭씠 뻼 샇씉湲곕룄 룓룷뒗 룓룷 떇꽭룷, 꽟쑀븘꽭룷, 긽뵾꽭룷(epithelial cell)濡 援ъ꽦릺뼱 엳떎(Fig. 2). 룓룷 떇꽭룷뒗 二쇰줈 룓룷뿉 긽二쇳븯硫 蹂묒썝洹좎씠굹 꽍硫댁꽟쑀 媛숈 쇅遺 臾쇱쭏쓣 룷떇븳떎. 꽟쑀븘꽭룷뒗 샇씉湲곕룄 룓룷쓽 긽뵾꽭룷 紐⑥꽭삁愿 궗씠뿉 議댁옱븯硫 肄쒕씪寃 꽟쑀瑜 빀꽦븯뒗 뿭븷쓣 븳떎. 긽뵾꽭룷뱾 以 듅엳 룓룷뿉 엳뒗 긽뵾꽭룷뒗 I삎 룓룷 긽뵾꽭룷(alveolar type I epithelial cell) II삎 룓룷 긽뵾꽭룷(alveolar type II epithelial cell)濡 굹닃 닔 엳뒗뜲, I삎 룓룷 긽뵾꽭룷뒗 룓룷 硫댁쟻쓽 遺遺꾩쓣 李⑥븯怨 엳쑝硫 II삎 룓룷 긽뵾꽭룷뒗 룓룷 꽭룷 닔쓽 遺遺꾩쓣 李⑥븳떎(Fig. 2). II삎 룓룷 긽뵾꽭룷뒗 I삎 룓룷 긽뵾꽭룷濡 遺꾪솕븯嫄곕굹 I삎 룓룷 긽뵾꽭룷 몴硫댁쓣 怨꾨㈃솢꽦젣 痢(surfactant layer)쑝濡 룄룷븳떎(Fig. 2). 룓룷 긽뵾꽭룷뒗 샇씉쑝濡 씤븳 湲곌퀎쟻 옄洹, 利, 뙺李쎄낵 씠셿쓣 諛쏅뒗 꽭룷씤뜲 씠 怨꾨㈃솢꽦젣痢듭 鍮꾩젙긽쟻씤 룓룷쓽 蹂삎 諛 젒옒쓣 諛⑹븯뒗 뿭븷쓣 븳떎(Yang et al., 2020).

꽍硫댁꽟쑀쓽 씉엯 諛 異뺤쟻怨 룓 꽟쑀솕쓽 吏꾪뻾 怨쇱젙

꽍硫댁꽟쑀쓽 씉엯쑝濡 씤븳 룓 議곗쭅 궡 異뺤쟻 怨쇱젙쓣 異붿쟻븯湲 쐞빐 紐⑤뜽 룞臾쇱뿉 湲곕컲븳 뿰援щ뱾씠 吏꾪뻾릺뼱솕떎. 씠瑜 넻빐 꽍硫댁꽟쑀쓽 쐞빐꽦쓣 寃곗젙븯뒗 뜲 엳뼱 꽍硫댁꽟쑀쓽 湲몄씠媛 以묒슂븳 슂씤씤 寃껋쓣 솗씤븯떎(Barlow et al., 2017). 湲몄씠媛 湲 꽍硫댁꽟쑀뒗 룓룷 떇꽭룷뿉 쓽븳 룷떇씠 옒 씪뼱굹吏 븡븘 젣嫄곕릺吏 븡怨 룓룷 궡 媛꾩쭏 議곗쭅(interstitial space)뿉 옣湲곌컙 異뺤쟻맂떎뒗 寃곌낵媛 蹂닿퀬릺뿀떎. 삉븳 湲몄씠媛 湲 꽍硫댁꽟쑀媛 遺윭吏硫댁꽌 꽭湲곌吏瑜 吏굹 샇씉湲곕룄뿉 룄떖븿쑝濡쒖뜥 꽍硫댁꽟쑀쓽 湲몄씠媛 湲몄닔濡 샇씉湲곕룄뿉 븳 쐞빐꽦씠 利앷븳떎뒗 寃곌낵룄 븣젮議뚮떎. 븯吏留 떎젣濡 꽍硫 솚寃쎌뿉 끂異쒕맂 궗엺쓽 寃쎌슦뿉뒗 뿬윭 湲몄씠쓽 꽍硫댁꽟쑀媛 샎빀맂 삎깭濡 씉엯릺吏留 吏湲덇퉴吏 吏꾪뻾릺뿀뜕 遺遺꾩쓽 룞臾 떎뿕뱾 듅젙 湲몄씠쓽 꽍硫댁꽟쑀留뚯쓣 궗슜븳 떎뿕씠씪뒗 젏뿉 엳뼱 떎젣濡 빞湲곕릺뒗 꽍硫댁쓽 쐞빐꽦쓣 젙솗븯寃 씠빐븯뒗뜲 븳怨꾧 엳떎.

꽍硫댁꽟쑀媛 鍮꾧컯쓣 넻빐 씉엯릺硫 10 μm 씠긽 湲몄씠쓽 꽟쑀뱾 쟾룄湲곕룄瑜 吏굹湲 쟾 젏븸痢듭뿉 엳뒗 꽟紐⑥쓽 슫룞뿉 쓽빐 遺遺 젣嫄곕맂떎(Kwan et al., 2010). 洹몃윭굹 湲몄씠媛 2 μm 씠븯쓽 誘몃┰옄 삎깭濡 씉엯릺嫄곕굹 꽍硫댁꽟쑀瑜 룷븿븳 遺꾩쭊뿉 吏냽쟻쑝濡 끂異쒕릺硫 꽍硫댁꽟쑀뒗 샇씉湲곕룄쓽 긽뵾꽭룷痢듭뿉 遺李⑸릺嫄곕굹 異뺤쟻맂 썑 뿼利앸컲쓳쓣 닔諛섑븯硫 긽뵾꽭룷瑜 愿넻븳떎(IARC Working Group, 2012). 씠 븣 異뺤쟻릺뒗 젙룄뒗 꽟쑀쓽 吏곴꼍怨 鍮꾨븯뿬 利앷븯怨 二쇰줈 異뺤쟻릺뒗 쐞移섎뒗 꽍硫댁꽟쑀쓽 援ъ“쟻 李⑥씠 븣臾몄뿉 궗臾몄꽍 怨꾩뿴 湲곕룄遺꾧린젏뿉, 媛곸꽟꽍 怨꾩뿴 룓룷愿뿉 二쇰줈 異뺤쟻맂떎. 異뺤쟻맂 꽍硫댁 湲곗껜쓽 씠룞寃쎈줈瑜 諛⑺빐븯湲곕룄 븯뒗뜲 씠 諛⑺빐 뒫젰 꽟쑀쓽 湲몄씠 鍮꾨븯뿬 利앷븳떎.

룓 꽟쑀솕뒗 꽍硫댁꽟쑀뿉 끂異쒕맂 샇씉湲곕룄 궡 媛꾩쭏 議곗쭅痢듭뿉꽌 씪뼱궃떎. 끂異 珥덇린뿉뒗 씪遺 샇씉湲곕룄뿉꽌留 꽟쑀솕媛 씪뼱굹吏留, 吏냽쟻쑝濡 꽍硫댁꽟쑀뿉 끂異쒕릺硫 씪遺 꽍硫댁꽟쑀媛 긽뵾꽭룷瑜 愿넻븯嫄곕굹 由쇳봽愿쓣 二쇰 議곗쭅쑝濡 씠룞븯뿬 룓 遺遺 쁺뿭뿉꽌 꽟쑀솕媛 吏꾪뻾맂떎. 理쒖쥌쟻쑝濡 湲곗껜援먰솚 湲곕뒫씠 쁽븯寃 뼥뼱吏뒗 꽍硫댄룓濡 씠뼱吏꾨떎(Fig. 2).

꽍硫댁꽟쑀媛 샇씉湲곕룄 議곗쭅뿉 誘몄튂뒗 꽭룷룆꽦

꽍硫댁꽟쑀媛 샇씉湲곕룄瑜 援ъ꽦븯뒗 꽭룷뿉 븳 꽭룷룆꽦쓣 빞湲고븯뒗 寃쎈줈뒗 겕寃 몢 媛吏濡 굹돇뼱吏꾨떎. 씠 몢 寃쎈줈뒗 怨듯넻쟻쑝濡 솢꽦궛냼醫낃낵 궗씠넗移댁씤뱾씠 愿뿬븯뿬 뿼利앸컲쓳, 꽭룷옄궡(apoptosis)쓣 씪쑝궎怨 理쒖쥌쟻쑝濡 꽟쑀븘꽭룷쓽 肄쒕씪寃 빀꽦쓣 珥됱쭊떆耳 꽭룷쇅湲곗쭏쓣 몢猿띻쾶 留뚮뱶뒗 꽟쑀솕濡 씠뼱吏꾨떎. 몢 寃쎈줈쓽 媛옣 겙 李⑥씠뒗 꽟쑀솕 怨쇱젙뿉꽌 룓룷 떇꽭룷쓽 吏곸젒쟻씤 愿뿬쓽 뿬遺씠떎.

泥 踰덉㎏ 寃쎈줈뿉꽌뒗 룓룷 떇꽭룷媛 愿뿬븯吏 븡 긽깭뿉꽌 꽍硫댁꽟쑀媛 샇씉湲곕룄쓽 긽뵾꽭룷瑜 吏곸젒 넀긽떆耳 솢꽦궛냼醫낃낵 궗씠넗移댁씤씠 諛쒖깮븳떎. 몢 踰덉㎏ 寃쎈줈뿉꽌뒗 꽍硫댁꽟쑀 젣嫄곗뿉 떎뙣븳 룓룷 떇꽭룷媛 궗硫명븯硫댁꽌 솢꽦궛냼醫낃낵 궗씠넗移댁씤씠 諛⑹텧맂떎. 궗씠넗移댁씤 議곗쭅씠 臾쇰━쟻 삉뒗 蹂묐━븰쟻 넀긽(삁, 꽭洹좎뿉 쓽븳 媛먯뿼)쓣 엯뿀쓣 븣 硫댁뿭꽭룷뿉꽌 遺꾨퉬릺뒗 꽭룷 궗씠쓽 떊샇쟾떖 臾쇱쭏씠怨 硫댁뿭諛섏쓳쓣 吏꾪뻾븯뒗뜲 以묒슂븳 뿭븷쓣 븳떎(Fajgenbaum and June, 2020).

꽍硫댁꽟쑀뒗 씠 몢 寃쎈줈瑜 넻븯뿬 理쒖쥌쟻쑝濡쒕뒗 룓 꽟쑀솕利앹쓣 쑀諛쒗븳떎. 룓 꽟쑀솕뒗 꽟쑀븘꽭룷뿉꽌 怨쇰룄븯寃 遺꾨퉬맂 肄쒕씪寃 떒諛깆쭏뱾씠 꽭룷쇅湲곗쭏뿉 異뺤쟻릺硫댁꽌 꽭룷쇅湲곗쭏씠 꽟쑀떒諛깆쭏濡 씤빐 몢爰쇱썙吏뒗 쁽긽씠떎. 샇씉湲곕룄뒗 룓룷瑜 몮윭떬 紐⑥꽭삁愿怨 吏곸젒쟻쑝濡 湲곗껜援먰솚쓣 븯뒗 以묒슂븳 뿭븷쓣 븳떎. 슜씠븳 湲곗껜援먰솚쓣 쐞빐 뻼 꽭룷痢듭쑝濡 릺뼱 엳뒗 룓룷 궡 媛꾩쭏 議곗쭅씠 꽟쑀솕濡 씤빐 몢爰쇱썙吏硫 湲곗껜 솗궛냽룄媛 쁽寃⑺븯寃 以꾩뼱뱺떎. 씠濡 씤븯뿬 썝솢븳 湲곗껜援먰솚씠 씪뼱굹吏 紐삵빐 샇씉 옣븷媛 굹궃떎.

꽍硫댁꽟쑀쓽 醫낅쪟, 湲몄씠, 異뺤쟻 諛 젣嫄 냽룄媛 꽍硫댁꽟쑀뿉 쓽븳 꽭룷룆꽦쓣 寃곗젙븯뒗 슂씤씠떎. 듅엳 꽍硫댁꽟쑀쓽 醫낅쪟瑜 젣쇅븳 굹癒몄 슂씤뱾 꽌濡 諛젒븯寃 뿰愿릺뼱 엳떎(Seaton, 1989). 利, 꽍硫댁꽟쑀쓽 湲몄씠媛 湲몃㈃ 쟾룄湲곕룄뿉 議댁옱븯뒗 꽟紐⑥ 젏븸뿉 쓽빐 쇅遺濡 諛곗텧맆 닔 엳뼱 샇씉湲곕룄뿉 룄떖븷 솗瑜좎씠 궙븘吏꾨떎. 븯吏留 씠윭븳 꽍硫댁꽟쑀媛 샇씉湲곕룄뿉 룄떖븷 寃쎌슦, 떇꽭룷媛 10 μm 씠긽 湲몄씠쓽 꽍硫댁꽟쑀瑜 돺寃 룷떇븷 닔 뾾뼱 옣湲곌컙 異뺤쟻맆 닔 엳떎. 諛섎㈃뿉 꽍硫댁꽟쑀쓽 湲몄씠媛 吏㏃쑝硫 샇씉湲곕룄뿉 돺寃 룄떖븷 닔 엳吏留 떇꽭룷뿉 쓽븳 젣嫄곕룄 鍮좊Ⅴ寃 씪뼱궃떎(Koerten et al., 1990). 꽍硫댁꽟쑀쓽 醫낅쪟 痢〓㈃뿉꽌뒗 씪諛섏쟻쑝濡 泥꽍硫, 媛덉꽍硫, 諛깆꽍硫 닚쑝濡 꽭룷룆꽦씠 굹궃떎. 媛곸꽟꽍 怨꾩뿴 꽍硫댁꽟쑀뒗 궗臾몄꽍 怨꾩뿴 꽍硫댁꽟쑀뿉 鍮꾪빐 샇씉湲곕룄뿉 뜑 옒 異뺤쟻맂떎. 삉븳 떇꽭룷媛 궗臾몄꽍 怨꾩뿴 꽍硫댁꽟쑀瑜 뜑 옒 젣嫄고븷 닔 엳뼱 媛곸꽟꽍怨 꽍硫댁꽟쑀媛 썾뵮 뜑 쑀빐븯떎.

룓룷 떇꽭룷媛 愿뿬븯吏 븡뒗 룓 꽟쑀솕 怨쇱젙

룓룷 議곗쭅뿉 룄떖븳 꽍硫댁꽟쑀뒗 議곗쭅 꽭룷留됱쓽 씪遺 닔슜泥대 솢꽦떆궎嫄곕굹 꽍硫댁꽟쑀 쑀옒쓽 泥 씠삩쓽 솚썝 怨쇱젙쓣 넻빐 떇꽭룷쓽 吏곸젒쟻씤 愿뿬 뾾씠룄 룓 꽟쑀솕瑜 珥덈옒븷 닔 엳떎(Fig. 3). 꽍硫댁꽟쑀뒗 룓룷 긽뵾꽭룷굹 꽟쑀븘꽭룷쓽 EGFR (epidermal growth factor receptor)瑜 솢꽦솕떆耳 MAPK (mitogen-activated protein kinase) 寃쎈줈瑜 넻빐 NF-κB (nuclear factor-kappa B) AP-1 (activator protein-1)怨 媛숈 쟾궗씤옄(transcription factor)뱾쓽 諛쒗쁽쓣 珥됱쭊븳떎(Shukla et al., 2003a). 씠뱾 쟾궗씤옄뒗 硫댁뿭꽭룷뱾쓽 利앹떇쓣 利앷떆궡쑝濡쒖뜥, TNF-α (tumor necrosis factor-α), IL-1β (interlukin-1β), IL-6 媛숈 뿼利앸컲쓳쓣 씪쑝궎뒗 二쇱슂 궗씠넗移댁씤뱾怨 MIP-1α (macrophage inflammatory protein-1α), MIP-3, IL-8怨 媛숈 耳紐⑥뭅씤(chemokine)쓽 遺꾨퉬瑜 利앸떆궓떎(Rappolee et al., 1988). 耳紐⑥뭅씤 떎瑜 硫댁뿭꽭룷뱾쓣 蹂묐 二쇰쑝濡 遺덈윭뱾씠怨 솢꽦솕떆耳 뿼利앸컲쓳쓣 利앺룺떆궎뒗뜲 몴쟻쑝濡 IL-8 샇以묒꽦 諛깊삁援(neutrophil)瑜 솢꽦솕븯怨 씠뱾쓣 뿼利 遺쐞濡 紐⑥뿬뱾寃 븳떎.

Fig. 3. Signaling cascades of the macrophage-independent fibrosis in the alveolar tissue. (A) The activation of the EGFR downstream by asbestos fibers leads to the increase in the level of cytokines or chemokines for the full-scale inflammation. (B) ROS generated in alveolar cells or fibroblasts by asbestos fibers damage gDNA and mtDNA, resulting in their apoptotic cell death (Abbreviations: EGFR, epidermal growth factor receptor; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor-kappa B; AP-1, activator protein-1; mtDNA, mitochondrial DNA; ROS, reactive oxygen species; TNF-α, tumor necrosis factor-α; IL, interleukin; MIP, macrophage inflammatory protein).

꽍硫댁꽟쑀쓽 援ъ“쟻 듅吏 븣臾몄뿉 Fe3+쓽 솚썝쓣 넻븳 Haber-Weiss 諛섏쓳怨 Fenton 諛섏쓳씠 씪뼱굹 솢꽦궛냼醫낆씠 諛쒖깮븯뒗뜲, 씠 솢꽦궛냼醫낆 빑 DNA (genomic DNA, gDNA) 誘명넗肄섎뱶由ъ븘 DNA (mitochondrial DNA, mtDNA)뿉 떖媛곹븳 넀긽쓣 二쇱뼱 寃곌뎅 꽭룷옄궡怨 룓 꽟쑀솕濡 吏꾪뻾맆 닔 엳떎(Shukla et al., 2003b). 삉븳 꽍硫댁꽟쑀뒗 엳뒪넠(histone)怨 넂 移쒗솕룄瑜 媛뽮퀬 엳뼱 꽍硫댁꽟쑀媛 빑 븞쑝濡 쑀엯릺硫 gDNA뿉 넀긽쓣 媛븳떎뒗 뿰援 寃곌낵媛 蹂닿퀬릺뿀떎(Jiang et al., 2008).

誘명넗肄섎뱶由ъ븘뿉 sirtuin (SIRT) 怨꾩뿴 以 븯굹씤 SIRT3 쑀쟾옄媛 엳떎. SIRT3 誘명넗肄섎뱶由ъ븘 궡뿉꽌 以묒슂븳 湲곕뒫쓣 븯뒗 뿬윭 떒諛깆쭏뱾쓣 깉븘꽭떥솕 떆궡쑝濡쒖뜥 솢꽦솕븯뿬 꽭룷쓽 臾쇱쭏궗瑜 珥됱쭊떆궓떎(Jablonski et al., 2017). 듅엳 SIRT3뒗 MnSOD (manganese superoxide dismutase)쓽 K68 깉븘꽭떥솕 mtOGG1 (oxoguanine DNA glycosylase1) K338/K441 깉븘꽭떥솕뿉 愿뿬븯뒗뜲 씠뱾 솢꽦궛냼醫낆뿉 븳 넀긽쓣 셿솕떆궎뒗 湲곕뒫쓣 븯뒗 쑀쟾옄뱾씠떎. 씠 븣 솢꽦궛냼醫낆뿉 쓽빐 SIRT3 媛숈 以묒슂븳 湲곕뒫쓣 븯뒗 쑀쟾옄媛 넀긽릺怨 솢꽦궛냼醫 젣嫄 湲곗쟾뿉 愿뿬븯뒗 뿬윭 쑀쟾옄뱾씠 李⑤濡 솢꽦쓣 엪쑝硫 솢꽦궛냼醫낆뿉 쓽븳 뵾빐媛 洹밸솕맂떎(Huang et al., 2012). 삉븳 꽍硫댁꽟쑀濡 諛쒖깮븳 솢꽦궛냼뿉 쓽븳 誘명넗肄섎뱶由ъ븘 쑀쟾옄쓽 넀긽 誘명넗肄섎뱶由ъ븘쓽 빑떖 湲곕뒫씤 꽭룷샇씉쓣 빐븷 닔 엳뼱 寃곌뎅 긽뵾꽭룷 떇꽭룷쓽 뿉꼫吏 怨좉컝뿉 쓽븳 궗硫몄쓣 쑀룄븷 닔 엳떎.

룓룷 떇꽭룷媛 愿뿬븯뒗 룓 꽟쑀솕 怨쇱젙

룓룷 떇꽭룷媛 泥대궡뿉 뱾뼱삩 꽍硫댁꽟쑀瑜 젒븯寃 릺硫 떇洹좎옉슜쓣 넻빐 꽍硫댁꽟쑀瑜 꽭룷 궡遺濡 媛졇삩떎. 씠 븣 궡룷맂 꽟쑀쓽 湲몄씠뒗 떇꽭룷쓽 깮議댁뿉 寃곗젙쟻씤 쁺뼢쓣 誘몄튇떎. 湲몄씠媛 湲 꽟쑀뒗 룷떇 씠썑 룓룷 떇꽭룷쓽 꽭룷吏덉뿉 셿쟾엳 궡룷릺吏 紐삵븯湲 븣臾몄뿉 룓룷 떇꽭룷쓽 꽭룷留됱쓣 뙆愿댁떆耳 꽭룷냼湲곌쓽 늻異쒖쓣 쑀룄븷 닔 엳떎(Schinwald and Donaldson, 2012). 븯吏留 씠뒗 룓룷 떇꽭룷뿉 빐 꽍硫댁꽟쑀媛 誘몄튂뒗 꽭룷룆꽦쓽 二쇱슂븳 슂씤 븘땲떎. 꽍硫댁꽟쑀뒗 β-tubulin, vimentin, lamin A/C, actin 벑쓽 꽭룷怨④꺽怨 꽭룷슫룞뿉 愿뿬븯뒗 떒諛깆쭏뱾怨 寃고빀븷 닔 엳떎. 꽭룷吏덈텇뿴 怨쇱젙뿉꽌 슫룞떒諛깆쭏뿉 遺李⑸맂 꽍硫댁꽟쑀뒗 룓룷 떇꽭룷쓽 꽭룷吏덈텇뿴쓣 諛⑺빐븳떎. 씠 븣 꽍硫댁꽟쑀쓽 湲몄씠 궡옱맂 諛⑺뼢씠 룓룷 떇꽭룷뿉 븳 꽭룷룆꽦쓣 寃곗젙븯뒗 以묒슂븳 슂씤씠 맂떎(Ishida et al., 2019). 湲몄씠媛 吏㏃ 꽍硫댁꽟쑀굹 꽭룷遺꾩뿴 諛⑺뼢뿉 빐 닔吏곸쑝濡 궡옱맂 꽍硫댁꽟쑀뒗 꽭룷吏덈텇뿴뿉 겙 臾몄젣瑜 씪쑝궎吏 븡吏留 湲몄씠媛 湲(10 μm 씠긽쓽) 꽍硫댁꽟쑀媛 꽭룷吏덈텇뿴 諛⑺뼢怨 룊뻾븯寃 궡옱맂떎硫 꽭룷吏덈텇뿴쓣 諛⑺빐븯뿬 뿼깋泥댁쓽 븞젙꽦쓣 빐븯嫄곕굹 씠닔꽦 룎뿰蹂씠瑜 삎꽦븷 닔 엳떎.

떇꽭룷뒗 룓 議곗쭅쓽 議곗쭅넀긽씠 씪뼱궗쓣 븣 뿼利앸컲쓳쓣 議곗젅븯뿬 議곗쭅쓽 닔꽑, 꽭룷 利앹떇, 꽭룷 옱깮뿉 愿젴븯怨 엳떎(Wynn et al., 2013). 룓룷 떇꽭룷媛 넀긽릺硫 뿼利앸컲쓳씠 븙솕맆 닔 엳떎. 떎젣濡 긽泥섍 諛쒖깮븳 썑 떇꽭룷 닔쓽 媛먯냼뒗 뿼利앸컲쓳쓣 湲됯꺽븯寃 媛먯냼떆궎뒗 寃껋쑝濡 솗씤릺뿀떎(Duffield et al., 2005). 뿼利앸컲쓳 넀긽맂 議곗쭅쓽 二쎌뼱媛뒗 꽭룷뱾뿉 쓽빐 쑀룄븳떎. 씠윭븳 뿼利앸컲쓳씠 젙긽쟻쑝濡 吏꾪뻾릺硫 넀긽맂 議곗쭅 쉶蹂듬릺吏留, 留뚯씪 씠 怨쇱젙씠 諛⑺빐瑜 諛쏄굅굹 吏泥대맂떎硫 꽟쑀솕瑜 씪쑝궎嫄곕굹 二쇰 젙긽꽭룷 諛 議곗쭅源뚯 넀긽떆耳 議곗쭅쓽 愿댁궗媛 吏꾪뻾맆 닔 엳떎(Wynn and Ramalingam, 2012).

룓룷 떇꽭룷媛 愿뿬븯吏 븡뒗 룓 꽟쑀솕 怨쇱젙怨 留덉갔媛吏濡 꽍硫댁꽟쑀뿉 쓽빐 넀긽맂 議곗쭅쓽 꽭룷뿉 쓽빐 媛곸쥌 궗씠넗移댁씤怨 耳紐⑥뭅씤 뱾씠 遺꾨퉬맂떎(Fig. 4B). 洹 寃곌낵 怨⑥닔뿉꽌 떇꽭룷쓽 쟾援ъ껜씤 떒빑援 삎꽦씠 쑀룄릺怨 紐⑥꽭삁愿쓣 넻빐 꽍硫댁꽟쑀뿉 끂異쒕맂 遺쐞濡 떇꽭룷뱾씠 紐⑥뿬뱾寃 맂떎(Wynn and Vannella, 2016). 洹 썑 솢꽦솕맂 떇꽭룷뒗 궗씠넗移댁씤쓣 遺꾨퉬븯뒗뜲, 씠뱾 궗씠넗移댁씤뱾 넀긽맂 議곗쭅쓽 蹂듦뎄瑜 쐞빐 떖븳 넀긽씠 씪뼱궃 꽭룷뒗 옄궡븯룄濡 紐낅졊븯怨 깉濡쒖슫 꽭룷쓽 利앹떇쓣 珥됱쭊븯硫, 떎瑜 硫댁뿭꽭룷뱾쓣 넀긽 遺쐞濡 遺덈윭紐⑥떎(Rappolee et al., 1988). 洹몃━怨 꽟쑀븘꽭룷瑜 옄洹뱁븯뿬 꽟쑀솕瑜 넻빐 넀긽씠 씪뼱궃 遺쐞瑜 留됰뒗떎. 븯吏留 씠 諛섏쓳뱾씠 鍮꾩젙긽쟻쑝濡 옣湲곌컙 吏냽맂떎硫 옄궡꽭룷뱾씠 利앷븯怨 洹멸쾬쑝濡 씤빐 룓룷쓽 鍮꾩젙긽쟻씤 꽟쑀솕媛 씪뼱궇 닔 엳떎. 꽭룷 利앹떇怨 遺꾪솕 怨쇱젙 삉븳 怨쇰룄븯寃 吏꾪뻾맂떎硫 룓룷 議곗쭅쓽 愿댁궗媛 씪뼱굹嫄곕굹 醫낆뼇씠 諛쒖깮븷 닔 엳떎.

Fig. 4. Two pathways to the pulmonary fibrosis in the alveolus. (A) The reactive oxygen or nitrogen species that can be produced by asbestos-exposed epithelial cells trigger the cascade of the fibrosis with no involvement of macrophages. (B) Macrophages that fail to uptake the asbestos fibers release cytokines and ROS during their cell death. ROS and cytokines released from the two pathways damage the alveolar cells while these molecule activate neutrophils and macrophages to recruit them to the damaged sites. Some cytokines and growth factors stimulate the fibroblast in the interstitial space to enhance the synthesis of collagen fibers, resulting in abnormally thickening the extracellular matrix (Abbreviations: ROS, reactive oxygen species; TNF-α.tumor necrosis factor-α; IL, interleukin; TGF-β, transforming growth factor-α; FGF, fibroblast growth factor).

뼢썑 뿰援 諛⑺뼢

꽍硫댁꽟쑀쓽 쐞빐꽦怨 愿젴븳 吏湲덇퉴吏쓽 뿬윭 뿰援щ뱾 룓 議곗쭅쓽 듅꽦怨 꽭룷 솚寃쎌쓽 듅꽦쓣 怨좊젮븯吏 븡 븳怨꾩젏쓣 媛吏꾨떎. 꽍硫댁꽟쑀쓽 샇씉怨꾩뿉 븳 蹂대떎 젙솗븳 쐞빐꽦 룊媛瑜 쐞빐 룓쓽 깮由ы븰쟻 듅꽦씠 諛섏쁺맂 떎뿕 紐⑤뜽 援ъ텞씠 븘슂븳 떎젙씠떎. 룓룷뒗 샇씉뿉 뵲瑜 吏냽쟻씤 湲곌퀎쟻 떊옣怨 씠셿쓣 諛섎났븯뒗 議곗쭅쑝濡, 룓 議곗쭅쓽 꽭룷뱾 씠윭븳 湲곌퀎쟻 옄洹 솚寃쏀븯뿉 넃뿬엳떎. 꽭룷 紐⑤뜽 뿰援ъ뿉꽌 湲곌퀎쟻 옄洹뱀쓽 議댁옱 뿬遺뿉 뵲씪 꽭룷쓽 諛섏쓳꽦씠 떖씪吏뒗 寃껋씠 蹂닿퀬릺怨 엳떎. 룓룷瑜 援ъ꽦븯뒗 꽭룷뱾씠 臾쇰━솕븰쟻 넀긽쓣 諛쏆 씠썑뿉 湲곌퀎쟻 옄洹뱀씠 二쇱뼱議뚯쓣 븣 DNA 넀긽 諛 뿼利앸컲쓳씠 媛냽솕릺뒗 寃곌낵媛 꽭룷二 샊 솚옄 떆猷뚮 넻빐 蹂닿퀬맂 諛 엳떎(Chapman et al., 2005; Blázquez-Prieto et al., 2021). 꽍硫댁꽟쑀뿉 끂異쒕릺吏 븡 II삎 룓룷 긽뵾꽭룷뒗 湲곌퀎쟻 옄洹뱀뿉 넃뿬 엳쓣 븣, 뜑 留롮 뼇쓽 怨꾨㈃솢꽦젣瑜 遺꾨퉬븯怨, 諛쒕떖 떒怨꾩뿉꽌 I삎 룓룷 긽뵾꽭룷濡 遺꾪솕븯뒗 뒫젰씠 而ㅼ뒗 寃껋씠 愿李곕릺뿀떎(Miroshnikova et al., 2017; Yang et al., 2020). 듅엳, 뿬윭 삎깭濡 룓 議곗쭅씠 넀긽맂 솚옄뿉寃 씤怨 샇씉湲(mechanical ventilator)瑜 넻빐 怨쇰룄븳 湲곌퀎쟻 옄洹뱀씠 二쇱뼱議뚯쓣 븣, 룓 꽟쑀솕 珥됱쭊뿉 뵲瑜 궗留앸쪧씠 利앷븯뒗 寃껋쑝濡 븣젮議뚮떎(Slutsky and Ranieri, 2013). 씠뒗 꽍硫댁꽟쑀뿉 끂異쒕맂 솚옄쓽 룓 議곗쭅씠 硫댁뿭諛섏쓳 諛 룓 꽟쑀솕媛 吏꾪뻾릺뒗 긽솴뿉꽌 씤怨 샇씉湲 泥섏튂媛 씠猷⑥뼱吏硫, 怨쇰룄븳 룓룷쓽 湲곌퀎쟻 뙺李쎄낵 씠셿쑝濡 씤빐 삤엳젮 꽍硫댁꽟쑀쓽 쐞빐꽦씠 뜑슧 利앸맆 닔 엳쓬쓣 떆궗븳떎. 뵲씪꽌, 씠뿉 愿븳 뼢썑 뿰援ъ 엫긽 쁽옣뿉꽌 吏냽쟻씤 紐⑤땲꽣留곸씠 蹂묓뻾맂떎硫 꽍硫댁꽟쑀 끂異쒖씠 썝씤씤 꽍硫댄룓, 븙꽦 以묓뵾醫, 룓븫솚옄뿉 븳 蹂대떎 쟻젅븳 移섎즺 諛 씤怨듯샇씉 쑀룄 룓 넀긽(ventilator-induced lung injury, VILI) 諛⑹瑜 쐞븳 씤怨 샇씉湲곗쓽 궗슜 諛⑹븞쓣 留덈젴븷 닔 엳쓣 寃껋씠떎.

쁽옱 二쇰줈 꽕移섎쪟 룞臾 紐⑤뜽뿉 븯뿬 떆뿕 湲 븞뿉 씪젙븳 냽룄쓽 꽍硫댁꽟쑀瑜 끂異쒖떆궓 썑 샇씉 떆媛꾩뿉 뵲瑜 룓 議곗쭅쓽 蹂묐━븰쟻 蹂솕瑜 遺꾩꽍븿쑝濡쒖뜥 꽍硫댁꽟쑀쓽 룓 룆꽦쓣 룊媛븯怨 엳떎. 븯吏留 쟾꽭怨꾩쟻 룞臾쇱떎뿕쑄由 媛뺥솕뿉 뵲瑜 3R (reduce, refine, replace) 젙梨낆뿉 뵲씪 룓 룆꽦 룞臾 떎뿕쓣 泥섑븷 닔 엳뒗 떎뿕踰 紐⑥깋씠 븘슂븳 떎젙씠떎. 肉먮쭔 븘땲씪 룞臾 紐⑤뜽쓽 룓 씤媛꾩쓽 룓 궗씠쓽 빐遺븰쟻/쑀쟾븰쟻/깮由ы븰쟻 李⑥씠濡 씤븯뿬 룞臾 紐⑤뜽 寃곌낵瑜 씤媛꾩뿉寃 쟻슜븯뒗뜲 엳뼱 븳怨 諛 遺덉씪移섍 諛쒖깮븯誘濡 醫뜑 吏곸젒쟻씤 씤媛 룓 룆꽦 룊媛 떆뒪뀥 媛쒕컻씠 븘슂븯떎. 씠뿉 理쒓렐뿉 씤媛 룓룷 議곗쭅쓽 삎깭 湲곕뒫쓣 泥댁쇅뿉꽌 옱援ъ꽦븳 alveolus-on-a-chip씠 媛쒕컻릺怨 엳떎(Huh et al., 2010; Roshanzadeh et al., 2020; Shrestha et al., 2020). 깮由ы븰怨 誘몄꽭쑀泥닿났븰(microfluidics)쓽 쑖빀쓣 넻빐 援ъ텞맂 alveolus-on-a-chip 씤媛꾩쓽 룓룷쓽 빐遺븰쟻 援ъ“, 湲곌퀎쟻 옄洹, 洹몃━怨 깮由ы븰/硫댁뿭븰쟻 湲곕뒫쓣 紐⑥궗븷 닔 엳떎. 씠瑜 씠슜븯뿬 꽍硫댁꽟쑀瑜 鍮꾨’븳 珥덈몄꽭엯옄, 씠瑜쇳뀒硫 珥덈몄꽭癒쇱, 굹끂뵆씪뒪떛, 뿉뼱濡쒖「 삎깭 怨듦린 遺쑀 臾쇱쭏뿉 븳 룓룷 룆꽦 뿰援щ 떆룄븳떎硫 湲곗〈쓽 룞臾 떎뿕 湲곕컲쓽 룆꽦 뿰援ъ쓽 븳怨꾨 蹂댁셿빐 굹媛 닔 엳쓣 寃껋씠떎. 삉븳 떒湲 샊 옣湲 꽍硫댁꽟쑀 끂異쒖뿉 뵲瑜 議곗쭅쓽 蹂솕瑜 떎떆媛 씠誘몄쭠怨 떎뼇븳 깮솕븰쟻 룊媛瑜 媛뒫븯寃 븿쑝濡쒖뜥 샇솄湲곕룄쓽 룓 꽟쑀솕 怨쇱젙怨 愿젴맂 遺꾩옄깮臾쇳븰쟻 湲곗쟾씠 醫뜑 紐낇솗븯寃 洹쒕챸맆 寃껋씠떎. 媛源뚯슫 誘몃옒뿉 룓쓽 빐遺븰쟻 援ъ꽦泥닿퀎(湲곌 > 湲곌吏 > 냼湲곌吏 > 룓룷)뿉 빐떦븯뒗 꽭룷瑜 궗슜븯뿬 3D cell printing怨 誘몄꽭쑀泥닿났븰쓣 젒紐⑹떆耳 "mini-lung"씠 泥댁쇅뿉꽌 援ъ텞맆 寃껋쑝濡 湲곕맂떎(Fig. 5). 씠瑜 넻빐 꽍硫댁꽟쑀媛 룓룷 肉먮쭔 븘땲씪 떎瑜 샇씉 議곗쭅뿉 誘몄튂뒗 쐞빐꽦源뚯 뙆븙븷 닔 엳怨, 룓 꽟쑀솕瑜 빐븷 닔 엳뒗 빟臾 깘깋(drug screening)怨 젙諛移섎즺(precision therapy) 媛쒕컻뿉 깉濡쒖슫 젒洹쇰쾿쑝濡 솢슜 媛뒫빐吏 寃껋쑝濡 湲곕븳떎.

Fig. 5. Schematic illustration of the mini-lung to be reconstructed by combining 3D cell printing and microfluidic approaches for mimicking the anatomical hierarchy of the human lung with the trachea, bronchi, bronchiole, and alveoli. The mini-lung system facilitate the risk assessment of air-born particles such as asbestos fibers, ultrafine dusts, nanoplastics, and aerosols.
寃 濡

蹂 珥앹꽕 꽍硫댁꽟쑀쓽 臾쇰━솕븰쟻 꽦吏덉쓣 꽕紐낇븯怨 꽍硫댁꽟쑀媛 룓룷 꽭룷뿉 誘몄튂뒗 룆꽦쓣 遺꾩옄깮臾쇳븰쟻 愿젏뿉꽌 湲곗닠븯떎. 씤泥 샇씉湲곕룄뿉 룄떖븳 꽍硫댁꽟쑀뿉 쓽븳 솢꽦궛냼醫낃낵 솢꽦吏덉냼醫낆 룓룷瑜 援ъ꽦븯뒗 꽭룷瑜 넀긽떆궗 肉 븘땲씪 룓룷 議곗쭅 궡 硫댁뿭꽭룷뱾쓣 吏냽쟻쑝濡 솢꽦솕떆궡쑝濡쒖뜥 理쒖쥌쟻쑝濡 룓 꽟쑀솕瑜 珥덈옒븳떎. 삉븳 꽍硫댁꽟쑀뿉 끂異쒕맂 룓룷 꽭룷뱾씠 쑀쟾泥 넀긽쓣 셿踰쏀엳 蹂듦뎄븯吏 紐삵븯뿬 븙꽦 醫낆뼇쑝濡 吏꾪뻾맆 닔 엳떎.

꽍硫댁꽟쑀瑜 룷븿븳 꽍硫 젣뭹뱾 洹 쐞빐꽦씠 諛앺吏湲곌퉴吏 吏냽쟻쑝濡 궗슜릺뿀怨 쁽옱 슦由щ굹씪뿉꽌 꽍硫닿굔異뺣Ъ쓣 빐泥댄븯뒗 옉뾽씠 吏꾪뻾릺怨 엳뼱 꽍硫 끂異쒖뿉 쓽븳 뵾빐쓽 쐞뿕꽦 뿬쟾엳 궓븘엳떎. 2007뀈 援궡뿉꽌 꽍硫 젣뭹 궗슜씠 湲덉릺뿀吏留 꽍硫댁꽟쑀濡 씤빐 諛쒖깮븯뒗 룓 꽟쑀솕뒗 30~40뀈쓽 옞蹂듦린瑜 넻빐 吏꾪뻾릺湲 븣臾몄뿉 怨쇨굅뿉 꽍硫댁꽟쑀뿉 끂異쒕릺뿀뜕 궗엺뱾뿉꽌 뼢썑 10~20뀈 씠궡 꽍硫댄룓, 븙꽦 以묓뵾醫, 룓븫怨 媛숈 吏덈퀝씠 諛쒖깮븷 媛뒫꽦씠 넂떎. 씠뿉 蹂 珥앹꽕쓣 넻빐 꽍硫댁꽟쑀쓽 샇씉湲곕룄뿉 븳 룆꽦 湲곗쟾쓣 씠빐븿쑝濡쒖뜥 꽍硫 끂異쒖뿉 븳 삁諛 諛 뵾빐옄 吏꾨떒 諛 移섎즺 諛⑹븞쓣 留덈젴븷 닔 엳쓣 寃껋씠떎. 꽍硫 젣뭹쓽 쟾硫 궗슜 湲덉 꽍硫 끂異쒖뿉 븳 洹쒖젣媛 떆뻾릺怨 엳뼱, 꽍硫댁꽟쑀뿉 쓽븳 샇씉湲 嫄닿컯 쐞삊 떎뻾엳 넻젣릺怨 엳떎怨 蹂 닔 엳떎. 븯吏留 理쒓렐 湲 以 珥덈몄꽭癒쇱, 룆꽦 臾쇱쭏씠 븿쑀맂 뿉뼱濡쒖「, 怨듦린 留ㅺ컻 諛붿씠윭뒪(airborne virus) 媛숈 슂씤뱾씠 援誘쇰뱾쓽 샇씉湲 嫄닿컯씠 쐞삊븯怨 엳뒗 떎젙씠떎. 씠뿉 뼢썑 뿰援ъ뿉꽌 泥댁쇅뿉꽌 씤泥 샇씉湲곗쓽 湲곕뒫怨 援ъ“瑜 紐⑥궗븳 alveolus-on-a-chip 샊 mini-lung 떆뒪뀥쓣 솢슜븯뿬 꽍硫댁꽟쑀瑜 鍮꾨’븳 뿬윭 슂씤뿉 쓽븳 룆꽦 뿰援ш 닔뻾맆 寃껋쑝濡 삁痢〓맂떎. 씠瑜 넻빐 쁽옱源뚯 紐낇솗븯寃 諛앺吏吏 븡 샇씉湲 議곗쭅쓽 솚寃 슂씤뿉 븳 諛섏쓳뿉 엳뼱 蹂대떎 紐낇솗븳 湲곗쟾 諛 떆怨듦컙쟻 씤怨쇨怨꾨 諛앺궪 닔 엳쑝由щ씪 쟾留앺븳떎.

ACKNOWLEDGEMENT

This work was supported by Chonnam National University (Grant number: 2020-3829) and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (Grant number: 2021R1F1A1049470).

CONFLICT OF INTEREST

The author has declared no conflict of interest.

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