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Intensive Care Medicine

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01-09-2004 | Review

Pulmonary endothelium in acute lung injury: from basic science to the critically ill

Authors: S. E. Orfanos, I. Mavrommati, I. Korovesi, C. Roussos

Published in: Intensive Care Medicine | Issue 9/2004

Abstract

Background

Pulmonary endothelium is an active organ possessing numerous physiological, immunological, and metabolic functions. These functions may be altered early in acute lung injury (ALI) and further contribute to the development of acute respiratory distress syndrome (ARDS). Pulmonary endothelium is strategically located to filter the entire blood before it enters the systemic circulation; consequently its integrity is essential for the maintenance of adequate homeostasis in both the pulmonary and systemic circulations. Noxious agents that affect pulmonary endothelium induce alterations in hemodynamics and hemofluidity, promote interactions with circulating blood cells, and lead to increased vascular permeability and pulmonary edema formation.

Objective

We highlight pathogenic mechanisms of pulmonary endothelial injury and their clinical implications in ALI/ARDS patients.

Simionescu M (1991) Lung endothelium: structure-function correlates. In: Crystal RG, West JB (eds) The Lung: scientific foundations. Raven, New York, pp 301–331

Bernard GR, Artigas A, Brigham KL, Carlet J, Falke A, Hudson L, Lamy M, LeGall JR, Morris A, Spragg R, the Consensus Committee (1994) The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 49:818–824

Pittet JF, Mackersie RC, Martin TR, Matthay MA (1997) Biological markers of acute lung injury: prognostic and pathogenic significance. Am J Respir Crit Care Med 155:1187–1205PubMed

Hassoun PM, Fanburg BL, Junod AF (1991) Metabolic functions. In: Crystal RG, West JB (eds) The lung: scientific foundations. Raven, New York, pp 313–327

Orfanos SE, Catravas JD (1993) Metabolic functions of the pulmonary endothelium. In: Yacoub M, Pepper J (eds) Annual review of cardiac surgery, 6th edn. Current Science, London, pp 52–59

Aaronson PI, Robertson TP, Ward JPT (2002) Endothelium-derived mediators and hypoxic pulmonary vasoconstriction. Respir Physiol Neurobiol 132:107–120CrossRefPubMed

Wort SJ, Evans TW (1999) The role of endothelium in modulating vascular control in sepsis and related conditions. Br Med Bull 55:30–48CrossRefPubMed

Park WY, Goodman RB, Steinberg KP, Ruzinski JT, Radella F 2nd, Park DR, Pugin J, Skerrett SJ, Hudson LD, Martin TR (2001) Cytokine balance in the lungs of patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 164:1896–1903PubMed

Meyrick B (1986) Pathology of the adult respiratory distress syndrome. Crit Care Clin 2:405–428PubMed

10.

Mutunga M, Fulton B, Bullock R, Batchelor A, Gascoigne A, Gillespie JI, Baudouin SV (2001) Circulating endothelial cells in patients with septic shock. Am J Respir Crit Care Med 163:195–200PubMed

11.

Oberholzer A, Oberholzer C, Moldawer LL (2000) Cytokine signalling-regulation of the immune response in normal and critically ill states. Crit Care Med 28 [Suppl 4]:N3–N12

12.

Mantovani A, Bussolini F, Introna M (1997) Cytokine regulation of endothelial cell function: from molecular level to the bedside. Immunol Today 18:231–239CrossRefPubMed

13.

Folkesson HG, Matthay MA, Hebert CA, Broaddus VC (1995) Acid aspiration induced lung injury in rabbits is mediated by interleukin-8 dependent mechanisms. J Clin Invest 96:107–116PubMed

14.

Laffon M, Pittet JF, Modelska K, Matthay MA, Young DM (1999) Interleukin-8 mediates injury from smoke inhalation to both the lung endothelial and the alveolar epithelial barriers in rabbits. Am J Respir Crit Care Med 160:1443–1449PubMed

15.

Pulido EJ, Shames BD, Pennica D, O’Leary RM, Bensard DD, Cain BS, McIntyre RC Jr (1999) Cardiotrophin-1 attenuates endotoxin-induced acute lung injury. J Surg Res 84:240–246CrossRefPubMed

16.

Kawamae KK, Pristine G, Chiumello D, Tremblay LN, Slutsky AS (2000) Partial liquid ventilation decreases serum tumor necrosis factor-α concentrations in a rat acid aspiration lung injury model. Crit Care Med 28:479–483CrossRefPubMed

17.

Kuebler WM, Parthasarathi K, Wang PM, Bhattacharya J (2000) A novel signalling mechanism between gas and blood compartments of the lung. J Clin Invest 105:905–913PubMed

18.

Grau GE, Mili N, Lou JN, Morel DR, Ricou B, Lucas R, Suter PM (1996) Phenotypic and functional analysis of pulmonary microvascular endothelial cells from patients with acute respiratory distress syndrome. Lab Invest 74:761–770PubMed

19.

Hashimoto S, Gon Y, Matsumoto K, Takeshita I, Takashi H (2001) N-acetylcysteine attenuates TNF-α induced p38 MAP kinase activation and p38 MAP kinase-mediated IL-8 production by human pulmonary vascular endothelial cells. Br J Pharmacol 132:270–276PubMed

20.

Matthay MA, Bhattacharya S, Gaver D, Ware LB, Lim LHK, Syrkina O, Eyal F, Hubmayr R (2002) Ventilator-induced lung injury: in vivo and in vitro mechanisms. Am J Physiol Lung Cell Mol Physiol 283:L678–L682PubMed

21.

Ranieri VM, Suter PM, Tortorella C, De Tullio R, Dayer JM, Brienza A, Bruno F, Slutsky AS (1999) Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome. JAMA 282:54–61CrossRefPubMed

22.

Frank JA, Gutierrez JA, Jones KD, Allen L, Dobbs L, Matthay MA (2002) Low tidal volume reduces epithelial and endothelial injury in acid-injured rat lungs. Am J Respir Crit Care Med 165:242–249PubMed

23.

Fan J, Ye RD, Malik AB (2001) Transcriptional mechanisms of acute lung injury. Am J Physiol Lung Cell Mol Physiol 281:L1037–L1050PubMed

24.

Blackwell TS, Christman JW (1997) The role of nuclear factor-kappa B in cytokine gene regulation. Am J Respir Cell Mol Biol 17:3–9PubMed

25.

Lum H, Roebuck KA (2001) Oxidant stress and endothelial cell dysfunction. Am J Physiol Cell Physiol 280:C719–C741PubMed

26.

Abraham E (2000) NF-κB activation Crit Care Med 28 [Suppl 4]:N100–N104

27.

Dschietzig T, Richter C, Pfannenschmidt G, Bartsch C, Laule M, Baumann G, Stangl K (2001) Dexamethasone inhibits stimulation of pulmonary endothelins by pro-inflammatory cytokines: possible involvement of a nuclear factor κB dependent mechanism. Intensive Care Med 27:751–756CrossRefPubMed

28.

Quinlan GJ, Upton RL (2002) Oxidant/antioxidant balance in acute respiratory distress syndrome. In: Evans TW, Griffiths MJD, Keogh BF (eds) European respiratory monograph: ARDS, vol 7, monograph 20. European Respiratory Society Journals, Sheffield, pp 33–46

29.

Bhatia M, Moochhala S (2004) Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. J Pathol 202:145–156CrossRefPubMed

30.

Haligren R, Samuelson T, Veng P, Modig I (1987) Eosinophil activation in the lung is related to lung damage in adult respiratory distress syndrome. Am Rev Respir Dis 135:639–642PubMed

31.

Rowen JL, Hyde DM, McDonald RJ (1990) Eosinophils cause acute edematous injury in isolated perfused rat lungs. Am Rev Respir Dis 142:215–220PubMed

32.

Hasleton PS, Roberts TE (1999) Adult respiratory distress syndrome-an update. Histopathology 34:285–294CrossRefPubMed

33.

Albelda SM, Smith CW, Ward PA (1994) Adhesion molecules and inflammatory injury. FASEB J 8:504–512PubMed

34.

Sheridan BC, McIntyre RC Jr, Moore EE, Meldrum DR, Agrafojo J, Fullerton DA (1997) Neutrophils mediate pulmonary vasomotor dysfunction in endotoxin-induced acute lung injury. J Trauma 42:391–397PubMed

35.

Folkesson HG, Matthay MA (1997) Inhibition of CD18 or CD11b attenuates acute lung injury after acid instillation in rabbits. J Appl Physiol 82:1743–1750CrossRefPubMed

36.

Moriuchi H, Zaha M, Fukumoto T, Yuizono T (1998) Activation of polymorphonuclear leukocytes in oleic acid-induced lung injury. Intensive Care Med 24:709–715CrossRefPubMed

37.

Azuma A, Takahashi S, Nose M, Araki K, Araki M, Takahashi T, Hirose M, Kawashima H, Miyasaka M, Kudoh S (2000) Role of E-selectin in bleomycin induced lung fibrosis in mice. Thorax 55:147–152CrossRefPubMed

38.

Sato N, Suzuki Y, Nishio K, Suzuki K, Naoki K, Takeshita K, Kudo H, Miyao N, Tsumura H, Serizawa H, Suematsu M, Yamaguchi K (2000) Roles of ICAM-1 for abnormal leukocyte recruitment in the microcirculation of bleomycin-induced fibrotic lung injury. Am J Respir Crit Care Med 161:1681–1688PubMed

39.

Folch E, Salas A, Panes J, Gelpi E, Roselo-Catafau J, Anderson DC, Navarro S, Pique JM, Fernandez-Cruz L, Closa D (1999) Role of P-selectin and ICAM-1 in pancreatitis-induced lung inflammation in rats. Ann Surg 230:792–799CrossRefPubMed

40.

Dry SM, Bechard KM, Milford EL, Churchill WH, Benjamin RJ (1999) The pathology of transfusion-related acute lung injury. Am J Clin Pathol 112:216–221PubMed

41.

Sakamaki F, Ishizaka A, Handa M, Fujishima S, Urano T, Sayama K, Nakamura H, Kanazawa M, Kawashiro T, Katayama M, Ikeda Y (1995) Soluble form of P-selectin in plasma is elevated in acute lung injury. Am J Respir Crit Care Med 151:1821–1826PubMed

42.

Moss M, Gillespie MK, Ackerson L, Moore FA, Moore EE, Parsons PE (1996) Endothelial cell activity varies in patients at risk for the adult respiratory distress syndrome. Crit Care Med 24:1782–1786CrossRefPubMed

43.

Donelly SC, Haslett C, Dransfield I, Robertson CE, Carter DC, Ross JA, Grant IS, Tedder TF (1994) Role of selectins in development of adult respiratory distress syndrome. Lancet 344:215–219CrossRefPubMed

44.

Xu N, Rahman A, Minshall RD, Tiruppathi C, Malik AB (2000) β₂-integrin blockade driven by E-selectin promoter prevents neutrophil sequestration and lung injury in mice. Circ Res 87:254–260PubMed

45.

Murray JF, Matthay MA, Luce JM, Flick MR (1988) An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis 138:720–723PubMed

46.

Sinclair DG, Braude S, Haslam PL, Evans TW (1994) Pulmonary endothelial permeability in patients with severe lung injury. Clinical correlates and natural history. Chest 106:535–539PubMed

47.

Dudek SM, Garcia JGN (2001) Cytoskeletal regulation of pulmonary vascular permeability. J Appl Physiol 91:1487–1500PubMed

48.

Thickett DR, Armstrong L, Christie SJ, Millar AB (2001) Vascular endothelial growth factor may contribute to increased vascular permeability in acute respiratory distress syndrome. Am J Respir Crit Care Med 164:1601–1605PubMed

49.

Block ER (1992) Pulmonary endothelial cell pathobiology: implications for acute lung injury. Am J Med Sci 304:136–144PubMed

50.

Morel Dr, Dargent F, Bachmann M, Suter PM, Junod AF (1985) Pulmonary extraction of serotonin and propranolol in patients with adult respiratory distress syndrome. Am Rev Respir Dis 132:479–484PubMed

51.

Carvalho AC, Bellman SM, Saullo VJ, Quinn D, Zapol WM (1982) Altered factor VIII in acute respiratory failure. N Engl J Med 307:1113–1119PubMed

52.

Sabharwal AK, Bajaj SP, Ameri A, Tricomi SM, Hyers TM, Dahms TE, Taylor FB, Bajaj MS (1995) Tissue factor pathway inhibitor and von Willebrand factor antigen levels in adult respiratory distress syndrome and in a primate model of sepsis. Am J Respir Crit Care Med 151:758–767PubMed

53.

Rubin DB, Wiener-Kronish JP, Murray JF, Green DR, Turner J, Luce JM, Montgomery AB, Marks JD, Matthay MA (1990) Elevated von Willebrand factor antigen is an early plasma predictor of acute lung injury in nonpulmonary sepsis syndrome. J Clin Invest 86:474–480PubMed

54.

Moss M, Ackerson L, Gillespie MK, Moore FA, Moore EE, Parsons PE (1995) Von Willebrand factor antigen levels are not predictive for the adult respiratory distress syndrome. Am J Respir Crit Care Med 151:15–20PubMed

55.

Bajaj MS, Tricomi SM (1999) Plasma levels of the three endothelial-specific proteins von Willebrand factor, tissue factor pathway inhibitor, and thrombomodulin do not predict the development of acute respiratory distress syndrome. Intensive Care Med 25:1259–1266PubMed

56.

Fisele B, Lamy M, Thijs LG, Keinecke H-O, Schuster H-P, Matthias FR, Fourrier F, Heinrichs H, Delvos U (1998) Antithrombin III in patients with severe sepsis. A randomized, placebo-controlled, double-blind multicenter trial plus a meta-analysis on all randomized, placebo-controlled, double-blind trials with antithrombin III in severe sepsis. Intensive Care Med 24:663–672CrossRefPubMed

57.

Uchiba M, Okajima K (1997) Antithrombin III (AT III) prevents LPS-induced pulmonary vascular injury: a novel biological activity of AT III. Semin Thromb Hemost 23:583–590PubMed

58.

McGregor IR, Perrie AM, Donnelly SC, Haslett C (1997) Modulation of human endothelial thrombomodulin by neutrophils and their release products. Am J Respir Crit Care Med 155:47–52PubMed

59.

Distefano G, Romeo MG, Betta P, Rodono A, Amato M (1998) Thrombomodulin serum levels in ventilated preterm babies with respiratory distress syndrome. Eur J Pediatr 157:327–330CrossRefPubMed

60.

Christoforidou-Solomidou M, Kennel S, Scherpereel A, Wiewrodt R, Solomides CC, Pietra GG, Murciano JC, Shah SA, Ischiropoulos H, Albelda SM, Muzykantov VR (2002) Vascular immunotargeting of glucose oxidase to the endothelial antigens induces distinct forms of oxidant acute lung injury: targeting to thrombomodulin, but not to PECAM-1, causes pulmonary thrombosis and neutrophil transmigration. Am J Pathol 160:1155–1169PubMed

61.

Grau GE, de Moerloose P, Bulla O, Lou J, Lei Z, Reber G, Mili N, Morel DR, Suter PM (1997) Haemostatic properties of human pulmonary and cerebral microvascular endothelial cells. Thromb Haemost 77:585–590PubMed

62.

Mawji IA, Mardsen PA (2003) Perturbations in paracrine control of the circulation: role of the endothelial-derived vasomediators, endothelin-1 and nitric oxide. Microsc Res Tech 60:46–58CrossRefPubMed

63.

Liu S, Crawley DE, Barnes PJ, Evans TW (1991) Endothelium derived relaxing factor inhibits hypoxic pulmonary vasoconstriction in rats. Am Rev Respir Dis 143:32–37PubMed

64.

Hart CM (1999) Nitric oxide in adult lung disease. Chest 115:1407–1417CrossRefPubMed

65.

Dupuis J, Stewart DJ, Cernacek P, Gosselin G (1996) Human pulmonary circulation is an important site for both clearance and production of endothelin-1. Circulation 94:1578–1584PubMed

66.

Langleben D, Demarchie M, Laporta D, Spanier AH, Schlesinger D, Stewart DJ (1993) Endothelin-1 in acute lung injury and the adult respiratory distress syndrome. Am Rev Respir Dis 148:1646–1650PubMed

67.

Sanai L, Haynes WG, MacKenzie A, Grant IS, Webb DJ (1996) Endothelin in sepsis and the adult respiratory distress syndrome. Intensive Care Med 22:52–56PubMed

68.

Moloney ED, Evans TW (2003) Pathophysiology and pharmacological treatment of pulmonary hypertension in acute respiratory distress syndrome. Eur Respir J 21:720–727PubMed

69.

Chen XL, Orfanos SE, Catravas JD (1992) Effects of indomethacin on PMA-induced pulmonary endothelial enzyme dysfunction in vivo. Am J Physiol 262:L153–L162PubMed

70.

Gust R, Kozlowski K, Stephenson AH, Schuster DP (1999) Role of cyclooxygenase-2 in oleic acid-induced acute lung injury. Am J Respir Crit Care Med 160:1165–1170PubMed

71.

Clavijo LC, Carter MB, Matheson PJ, Wills-Frank LA, Wilson MA, Wead WB, Garrison RN (2000) Platelet activating factor and bacteremia-induced pulmonary hypertension. J Surg Res 88:173–180CrossRefPubMed

72.

Orfanos SE, Kotanidou K, Roussos C (2002) Pulmonary endothelial angiotensin converting enzyme in lung injury. In: Vincent JL (ed) 2002 Yearbook of intensive care and emergency medicine. Springer, Berlin Heidelberg New York; pp 100–110

73.

Linz W, Wohlfart P, Scholkens BA, Malinski T, Wiemer G (1999) Interactions among ACE, kinins and NO. Cardiovasc Res 43:549–561CrossRefPubMed

74.

McCloud L, Parkerson JB, Freant L, Hoffman WH, Catravas JD (2004) β-hydroxybutyrate induces acute pulmonary endothelial dysfunction in rabbits. Exp Lung Res 30:193-206CrossRefPubMed

75.

Kohlstedt K, Brandes RP, Muller-Esterl W, Busse R, Fleming I (2004) Angiotensin converting enzyme is involved in outside-in signalling in endothelial cells. Circ Res 94:60–67CrossRefPubMed

76.

Ryan US, Ryan JW, Whitaker C, Chiu A. (1976) Localization of angiotensin-converting enzyme (kinase II). Immunocytochemistry and immunofluorescence. Tissue Cell 8:125–146PubMed

77.

Orfanos SE, Langleben D, Khoury J, Schlesinger RD, Dragatakis L, Roussos C, Ryan JW, Catravas JD (1999) Pulmonary capillary endothelium-bound angiotensin converting enzyme activity in humans. Circulation 99:1593–1599PubMed

78.

Casey L, Krieger B, Kohler J, Rice C, Oparil S, Szidon P (1982) Decreased serum angiotensin converting enzyme in adult respiratory distress syndrome associated with sepsis: a preliminary report. Crit Care Med 9:651–654

79.

Lazo JS, Catravas JD, Gillis CN (1981) Reduction in rabbit serum and pulmonary angiotensin converting enzyme after subacute bleomycin treatment. Biochem Pharmacol 30:2577–2584CrossRefPubMed

80.

Dobuler KJ, Catravas JD, Gillis CN (1982) Early detection of oxygen-induced lung injury in conscious rabbits: reduced in vivo activity of angiotensin converting enzyme and removal of 5-hydoxytryptamine. Am Rev Respir Dis 126:534–539PubMed

81.

Ehrhart IC, Orfanos SE, McCloud LL, Sickles DW, Hoffman WF, Catravas JD (1999) Vascular recruitment increases evidence of lung injury. Crit Care Med 27:120–129CrossRefPubMed

82.

Orfanos SE, Chen XL, Burch SE, Ryan JW, Chunk AYK, Catravas JD (1994) Radiation-induced early pulmonary endothelial ectoenzyme dysfunction in vivo: effect of indomethacin. Toxicol Appl Pharmacol 124:112–122CrossRefPubMed

83.

Catravas JD, Burch SE, Sprulock BO, Mills LR (1988) Early effects of ionising radiation on pulmonary endothelial angiotensin converting enzyme and 5’-nucleotidase, in vivo. Toxicol Appl Pharmacol 94:342–355PubMed

84.

Atochina EN, Muzykantov VR, Al-Medhi AB, Danilov SM, Fisher AB (1997) Normotoxic lung ischemia/reperfusion accelerates shedding of angiotesin converting enzyme from the pulmonary endothelium. Am J Respir Crit Care Med 156:1114–1119PubMed

85.

Orfanos SE, Armaganidis A, Glynos C, Psevdi E, Kaltsas P, Sarafidou P, Catravas JD, Dafni UG, Langleben D, Roussos C (2000) Pulmonary capillary endothelium-bound angiotensin converting enzyme activity in acute lung injury. Circulation 102:2011–2018PubMed

86.

Marshall RP, Webb S, Bellingan GJ, Montgomery HE, Chaudhari B, McAnulty RJ, Humphries SE, Hill MR, Laurent GJ (2002) Angiotensin converting enzyme insertion/deletion polymorphism is associated with susceptibility and outcome in acute respiratory distress syndrome. Am J Respir Crit Care Med 166:646–650CrossRefPubMed

87.

Groeneveld ABJ (2003) Vascular pharmacology of acute lung injury and acute respiratory distress syndrome. Vascul Pharmacol 39:247–256CrossRef

88.

Wang Q, Pfeiffer GR, Stevens T, Doerschuck CM (2002) Lung microvascular and arterial endothelial cells differ in their responses to intercellular adhesion molecule-1 ligation. Am J Respir Crit Care Med 166:872–877CrossRefPubMed

89.

Parthasarathi K, Ichimura H, Bhattacharya J (2003) Septal capillaries communicate pro-inflammatory signals to downstream vascular segments in lung (abstract). Am J Respir Crit Care Med 167:A121

90.

Matthay MA, Zimmerman GA, Esmon C, Bhattacharya J, Coller B, Doerschuck CM, Floros J, Gimbrone MA Jr, Hoffman E, Hubmayr RD, Leppert M, Matalon S, Munford R, Parsons P, Slutsky AS, Tracey KJ, Ward P, Gail DB, Harabin AL (2003) Future research directions in acute lung injury. Summary of a National Heart, Lung and Blood Institute working group Am J Respir Crit Care Med 167:1027–1035

Title: Pulmonary endothelium in acute lung injury: from basic science to the critically ill
Authors: S. E. Orfanos
I. Mavrommati
I. Korovesi
C. Roussos
Publication date: 01-09-2004
Publisher: Springer-Verlag
Published in: Intensive Care Medicine / Issue 9/2004
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-004-2370-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Pulmonary endothelium in acute lung injury: from basic science to the critically ill

Abstract

Background

Objective

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Objective

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