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Macrophage-epithelial interactions in pulmonary alveoli

Abstract

Alveolar macrophages have been investigated for years by approaches involving macrophage extraction from the lung by bronchoalveolar lavage, or by cell removal from lung tissue. Since extracted macrophages are studied outside their natural milieu, there is little understanding of the extent to which alveolar macrophages interact with the epithelium, or with one another to generate the lung’s innate immune response to pathogen challenge. Here, we review new evidence of macrophage-epithelial interactions in the lung, and we address the emerging understanding that the alveolar epithelium plays an important role in orchestrating the macrophage-driven immune response.

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References

  1. 1.

    Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ, Hudson LD (2005) Incidence and outcomes of acute lung injury. N Engl J Med 353(16):1685–93

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Janssen WJ, Barthel L, Muldrow A, Oberley-Deegan RE, Kearns MT, Jakubzick C, Henson PM (2011) Fas determines differential fates of resident and recruited macrophages during resolution of acute lung injury. Am J Respir Crit Care Med 184(5):547–60

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Maus UA, Janzen S, Wall G, Srivastava M, Blackwell TS, Christman JW, Seeger W, Welte T, Lohmeyer J (2006) Resident alveolar macrophages are replaced by recruited monocytes in response to endotoxin-induced lung inflammation. Am J Respir Cell Mol Biol 35(2):227–35

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Aggarwal NR, King LS, D’Alessio FR (2014) Diverse macrophage populations mediate acute lung inflammation and resolution. Am J Physiol Lung Cell Mol Physiol 306(8):L709–25

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Herold S, Tabar TS, Janssen H, Hoegner K, Cabanski M, Lewe-Schlosser P, Albrecht J, Driever F, Vadasz I, Seeger W, Steinmueller M, Lohmeyer J (2011) Exudate macrophages attenuate lung injury by the release of IL-1 receptor antagonist in gram-negative pneumonia. Am J Respir Crit Care Med 183(10):1380–90

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Guilliams M, De Kleer I, Henri S, Post S, Vanhoutte L, De Prijck S, Deswarte K, Malissen B, Hammad H, Lambrecht BN (2013) Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF. J Exp Med 210(10):1977–92

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Gomez Perdiguero E, Klapproth K, Schulz C, Busch K, Azzoni E, Crozet L, Garner H, Trouillet C, de Bruijn MF, Geissmann F, Rodewald HR (2015) Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors. Nature 518(7540):547–51

    Article  CAS  PubMed  Google Scholar 

  8. 8.

    Ginhoux F (2014) Fate PPAR-titioning: PPAR-gamma ‘instructs’ alveolar macrophage development. Nat Immunol 15(11):1005–7

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Schulz C, Gomez Perdiguero E, Chorro L, Szabo-Rogers H, Cagnard N, Kierdorf K, Prinz M, Wu B, Jacobsen SE, Pollard JW, Frampton J, Liu KJ, Geissmann F (2012) A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 336(6077):86–90

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Mercer RR, Russell ML, Crapo JD (1994) Alveolar septal structure in different species. J Appl Physiol (1985) 77(3):1060–6

    CAS  Google Scholar 

  11. 11.

    Stone KC, Mercer RR, Gehr P, Stockstill B, Crapo JD (1992) Allometric relationships of cell numbers and size in the mammalian lung. Am J Respir Cell Mol Biol 6(2):235–43

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Westphalen K, Gusarova GA, Islam MN, Subramanian M, Cohen TS, Prince AS, Bhattacharya J (2014) Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity. Nature 506(7489):503–6

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Geiser M, Serra AL, Cruz-Orive LM, Baumann M, Im Hof V, Gehr P (1995) Efficiency of airway macrophage recovery by bronchoalveolar lavage in hamsters: a stereological approach. Eur Respir J 8(10):1712–8

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Goulding J, Godlee A, Vekaria S, Hilty M, Snelgrove R, Hussell T (2011) Lowering the threshold of lung innate immune cell activation alters susceptibility to secondary bacterial superinfection. J Infect Dis 204(7):1086–94

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Frank JA, Wray CM, McAuley DF, Schwendener R, Matthay MA (2006) Alveolar macrophages contribute to alveolar barrier dysfunction in ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol 291(6):L1191–8

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Kirby AC, Coles MC, Kaye PM (2009) Alveolar macrophages transport pathogens to lung draining lymph nodes. J Immunol 183(3):1983–9

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Perlman CE, Bhattacharya J (2007) Alveolar expansion imaged by optical sectioning microscopy. J Appl Physiol (1985) 103(3):1037–44

    Article  Google Scholar 

  18. 18.

    Clements JA (1997) Lung surfactant: a personal perspective. Annu Rev Physiol 59:1–21

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Wright JR (2005) Immunoregulatory functions of surfactant proteins. Nat Rev Immunol 5(1):58–68

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Suzuki T, Arumugam P, Sakagami T, Lachmann N, Chalk C, Sallese A, Abe S, Trapnell C, Carey B, Moritz T, Malik P, Lutzko C, Wood RE, Trapnell BC (2014) Pulmonary macrophage transplantation therapy. Nature 514(7523):450–4

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Bastacky J, Lee CY, Goerke J, Koushafar H, Yager D, Kenaga L, Speed TP, Chen Y, Clements JA (1995) Alveolar lining layer is thin and continuous: low-temperature scanning electron microscopy of rat lung. J Appl Physiol (1985) 79(5):1615–28

    CAS  Google Scholar 

  22. 22.

    Lindert J, Perlman CE, Parthasarathi K, Bhattacharya J (2007) Chloride-dependent secretion of alveolar wall liquid determined by optical-sectioning microscopy. Am J Respir Cell Mol Biol 36(6):688–96

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Ashino Y, Ying X, Dobbs LG, Bhattacharya J (2000) [Ca(2+)](i) oscillations regulate type II cell exocytosis in the pulmonary alveolus. Am J Physiol Lung Cell Mol Physiol 279(1):L5–13

    CAS  PubMed  Google Scholar 

  24. 24.

    Kuebler WM, Parthasarathi K, Wang PM, Bhattacharya J (2000) A novel signaling mechanism between gas and blood compartments of the lung. J Clin Invest 105(7):905–13

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Patel BV, Wilson MR, O’Dea KP, Takata M (2013) TNF-induced death signaling triggers alveolar epithelial dysfunction in acute lung injury. J Immunol 190(8):4274–82

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Ahn DS, Parker D, Planet PJ, Nieto PA, Bueno SM, Prince A (2014) Secretion of IL-16 through TNFR1 and calpain-caspase signaling contributes to MRSA pneumonia. Mucosal Immunol 7(6):1366–74

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Tomita T, Sakurai Y, Ishibashi S, Maru Y (2011) Imbalance of Clara cell-mediated homeostatic inflammation is involved in lung metastasis. Oncogene 30(31):3429–39

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Thorley AJ, Grandolfo D, Lim E, Goldstraw P, Young A, Tetley TD (2011) Innate immune responses to bacterial ligands in the peripheral human lung—role of alveolar epithelial TLR expression and signalling. PLoS One 6(7), e21827

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Guervilly C, Lacroix R, Forel JM, Roch A, Camoin-Jau L, Papazian L, Dignat-George F (2011) High levels of circulating leukocyte microparticles are associated with better outcome in acute respiratory distress syndrome. Crit Care 15(1):R31

    Article  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Yuana Y, Sturk A, Nieuwland R (2013) Extracellular vesicles in physiological and pathological conditions. Blood Rev 27(1):31–9

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Hess C, Sadallah S, Hefti A, Landmann R, Schifferli JA (1999) Ectosomes released by human neutrophils are specialized functional units. J Immunol 163(8):4564–73

    CAS  PubMed  Google Scholar 

  32. 32.

    Bastarache JA, Fremont RD, Kropski JA, Bossert FR, Ware LB (2009) Procoagulant alveolar microparticles in the lungs of patients with acute respiratory distress syndrome. Am J Physiol Lung Cell Mol Physiol 297(6):L1035–41

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Mutschler DK, Larsson AO, Basu S, Nordgren A, Eriksson MB (2002) Effects of mechanical ventilation on platelet microparticles in bronchoalveolar lavage fluid. Thromb Res 108(4):215–20

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Bourdonnay E, Zaslona Z, Penke LR, Speth JM, Schneider DJ, Przybranowski S, Swanson JA, Mancuso P, Freeman CM, Curtis JL, Peters-Golden M (2015) Transcellular delivery of vesicular SOCS proteins from macrophages to epithelial cells blunts inflammatory signaling. J Exp Med 212(5):729–42

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Westphalen K, Monma E, Islam MN, Bhattacharya J (2012) Acid contact in the rodent pulmonary alveolus causes proinflammatory signaling by membrane pore formation. Am J Physiol Lung Cell Mol Physiol 303(2):L107–16

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Quintero PA, Knolle MD, Cala LF, Zhuang Y, Owen CA (2010) Matrix metalloproteinase-8 inactivates macrophage inflammatory protein-1 alpha to reduce acute lung inflammation and injury in mice. J Immunol 184(3):1575–88

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Shanley TP, Schmal H, Friedl HP, Jones ML, Ward PA (1995) Role of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in acute lung injury in rats. J Immunol 154(9):4793–802

    CAS  PubMed  Google Scholar 

  38. 38.

    Calandra T, Roger T (2003) Macrophage migration inhibitory factor: a regulator of innate immunity. Nat Rev Immunol 3(10):791–800

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Calandra T, Bernhagen J, Mitchell RA, Bucala R (1994) The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor. J Exp Med 179(6):1895–902

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Kawai T, Akira S (2006) TLR signaling. Cell Death Differ 13(5):816–25

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Kobayashi K, Hernandez LD, Galan JE, Janeway CA Jr, Medzhitov R, Flavell RA (2002) IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 110(2):191–202

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    Kawai T, Adachi O, Ogawa T, Takeda K, Akira S (1999) Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 11(1):115–22

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H, Takeuchi O, Sugiyama M, Okabe M, Takeda K, Akira S (2003) Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 301(5633):640–3

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Hoebe K, Du X, Georgel P, Janssen E, Tabeta K, Kim SO, Goode J, Lin P, Mann N, Mudd S, Crozat K, Sovath S, Han J, Beutler B (2003) Identification of Lps2 as a key transducer of MyD88-independent TIR signalling. Nature 424(6950):743–8

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Togbe D, Schnyder-Candrian S, Schnyder B, Doz E, Noulin N, Janot L, Secher T, Gasse P, Lima C, Coelho FR, Vasseur V, Erard F, Ryffel B, Couillin I, Moser R (2007) Toll-like receptor and tumour necrosis factor dependent endotoxin-induced acute lung injury. Int J Exp Pathol 88(6):387–91

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Dagvadorj J, Shimada K, Chen S, Jones HD, Tumurkhuu G, Zhang W, Wawrowsky KA, Crother TR, Arditi M (2015) Lipopolysaccharide induces alveolar macrophage necrosis via CD14 and the P2X7 receptor leading to interleukin-1alpha release. Immunity 42(4):640–53

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Iwami KI, Matsuguchi T, Masuda A, Kikuchi T, Musikacharoen T, Yoshikai Y (2000) Cutting edge: naturally occurring soluble form of mouse Toll-like receptor 4 inhibits lipopolysaccharide signaling. J Immunol 165(12):6682–6

    CAS  Article  PubMed  Google Scholar 

  48. 48.

    Yuk JM, Kim TS, Kim SY, Lee HM, Han J, Dufour CR, Kim JK, Jin HS, Yang CS, Park KS, Lee CH, Kim JM, Kweon GR, Choi HS, Vanacker JM, Moore DD, Giguere V, Jo EK (2015) Orphan nuclear receptor ERRalpha controls macrophage metabolic signaling and A20 expression to negatively regulate TLR-induced inflammation. Immunity 43(1):80–91

    CAS  Article  PubMed  Google Scholar 

  49. 49.

    Sheedy FJ, Palsson-McDermott E, Hennessy EJ, Martin C, O’Leary JJ, Ruan Q, Johnson DS, Chen Y, O’Neill LA (2010) Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nat Immunol 11(2):141–7

    CAS  Article  PubMed  Google Scholar 

  50. 50.

    O’Neill LA, Sheedy FJ, McCoy CE (2011) MicroRNAs: the fine-tuners of Toll-like receptor signalling. Nat Rev Immunol 11(3):163–75

    Article  CAS  PubMed  Google Scholar 

  51. 51.

    Androulidaki A, Iliopoulos D, Arranz A, Doxaki C, Schworer S, Zacharioudaki V, Margioris AN, Tsichlis PN, Tsatsanis C (2009) The kinase Akt1 controls macrophage response to lipopolysaccharide by regulating microRNAs. Immunity 31(2):220–31

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Taganov KD, Boldin MP, Chang KJ, Baltimore D (2006) NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A 103(33):12481–6

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  53. 53.

    Wesche H, Gao X, Li X, Kirschning CJ, Stark GR, Cao Z (1999) IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family. J Biol Chem 274(27):19403–10

    CAS  Article  PubMed  Google Scholar 

  54. 54.

    Lang T, Mansell A (2007) The negative regulation of Toll-like receptor and associated pathways. Immunol Cell Biol 85(6):425–34

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Kuo CC, Lin WT, Liang CM, Liang SM (2006) Class I and III phosphatidylinositol 3′-kinase play distinct roles in TLR signaling pathway. J Immunol 176(10):5943–9

    CAS  Article  PubMed  Google Scholar 

  56. 56.

    Rowlands DJ, Islam MN, Das SR, Huertas A, Quadri SK, Horiuchi K, Inamdar N, Emin MT, Lindert J, Ten VS, Bhattacharya S, Bhattacharya J (2011) Activation of TNFR1 ectodomain shedding by mitochondrial Ca2+ determines the severity of inflammation in mouse lung microvessels. J Clin Invest 121(5):1986–99

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  57. 57.

    Vadasz I, Dada LA, Briva A, Trejo HE, Welch LC, Chen J, Toth PT, Lecuona E, Witters LA, Schumacker PT, Chandel NS, Seeger W, Sznajder JI (2008) AMP-activated protein kinase regulates CO2-induced alveolar epithelial dysfunction in rats and human cells by promoting Na,K-ATPase endocytosis. J Clin Invest 118(2):752–62

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Tobimatsu T, Fujisawa H (1989) Tissue-specific expression of four types of rat calmodulin-dependent protein kinase II mRNAs. J Biol Chem 264(30):17907–12

    CAS  PubMed  Google Scholar 

  59. 59.

    Liu Z, Bone N, Jiang S, Park DW, Tadie JM, Deshane J, Rodriguez CA, Pittet JF, Abraham E, Zmijewski JW (2015) AMP-activated protein kinase and glycogen synthase kinase 3beta modulate the severity of sepsis-induced lung injury. Mol Med

  60. 60.

    Risso G, Blaustein M, Pozzi B, Mammi P, Srebrow A (2015) Akt/PKB: one kinase, many modifications. Biochem J 468(2):203–14

    CAS  Article  PubMed  Google Scholar 

  61. 61.

    Kumar S, Xu J, Kumar RS, Lakshmikanthan S, Kapur R, Kofron M, Chrzanowska-Wodnicka M, Filippi MD (2014) The small GTPase Rap1b negatively regulates neutrophil chemotaxis and transcellular diapedesis by inhibiting Akt activation. J Exp Med 211(9):1741–58

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Hsu AC, Starkey MR, Hanish I, Parsons K, Haw TJ, Howland LJ, Barr I, Mahony JB, Foster PS, Knight DA, Wark PA, Hansbro PM (2015) Targeting PI3K-p110alpha suppresses influenza virus infection in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 191(9):1012–23

    CAS  Article  PubMed  Google Scholar 

  63. 63.

    Angulo O, Vadas F, Garcon E, Banham-Hall V, Plagnol TR, Leahy H, Baxendale T, Coulter J, Curtis C, Wu K, Blake-Palmer O, Perisic D, Smyth M, Maes C, Fiddler J, Juss D, Cilliers G, Markelj A, Chandra G, Farmer A, Kielkowska J, Clark S, Kracker M, Debre C, Picard I, Pellier N, Jabado JA, Morris G, Barcenas-Morales A, Fischer L, Stephens P, Hawkins JC, Barrett M, Abinun M, Clatworthy A, Durandy R, Doffinger ER, Chilvers AJ, Cant D, Kumararatne K, Okkenhaug RL, Williams A, Condliffe S (2013) Nejentsev, phosphoinositide 3-kinase delta gene mutation predisposes to respiratory infection and airway damage. Science 342(6160):866–71

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  64. 64.

    Ling H, Gray CB, Zambon AC, Grimm M, Gu Y, Dalton N, Purcell NH, Peterson K, Brown JH (2013) Ca2+/Calmodulin-dependent protein kinase II delta mediates myocardial ischemia/reperfusion injury through nuclear factor-kappaB. Circ Res 112(6):935–44

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Chen BC, Wu WT, Ho FM, Lin WW (2002) Inhibition of interleukin-1b-induced NF-kB activation by calcium/calmodulin-dependent protein kinase kinase occurs through Akt activation associated with interleukin-1 receptor-associated kinase phosphorylation and uncoupling of MyD88. J Biol Chem 277:24169–79

  66. 66.

    Yano S, Tokumitsu H, Soderling TR (1998) Calcium promotes cell survival through CaM-K kinase activation of the protein-kinase-B pathway. Nature 396(6711):584–7

    CAS  Article  PubMed  Google Scholar 

  67. 67.

    Yano S, Morioka M, Kuratsu J, Fukunaga K (2005) Functional proteins involved in regulation of intracellular Ca(2+) for drug development: role of calcium/calmodulin-dependent protein kinases in ischemic neuronal death. J Pharmacol Sci 97(3):351–4

    CAS  Article  PubMed  Google Scholar 

  68. 68.

    Zhao M, Fernandez LG, Doctor A, Sharma AK, Zarbock A, Tribble CG, Kron IL, Laubach VE (2006) Alveolar macrophage activation is a key initiation signal for acute lung ischemia-reperfusion injury. Am J Physiol Lung Cell Mol Physiol 291(5):L1018–26

    CAS  Article  PubMed  Google Scholar 

  69. 69.

    Dhaliwal K, Scholefield E, Ferenbach D, Gibbons M, Duffin R, Dorward DA, Morris AC, Humphries D, MacKinnon A, Wilkinson TS, Wallace WA, van Rooijen N, Mack M, Rossi AG, Davidson DJ, Hirani N, Hughes J, Haslett C, Simpson AJ (2012) Monocytes control second-phase neutrophil emigration in established lipopolysaccharide-induced murine lung injury. Am J Respir Crit Care Med 186(6):514–24

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  70. 70.

    Bem RA, Farnand AW, Wong V, Koski A, Rosenfeld ME, van Rooijen N, Frevert CW, Martin TR, Matute-Bello G (2008) Depletion of resident alveolar macrophages does not prevent Fas-mediated lung injury in mice. Am J Physiol Lung Cell Mol Physiol 295(2):L314–25

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  71. 71.

    Elder A, Johnston C, Gelein R, Finkelstein J, Wang Z, Notter R, Oberdorster G (2005) Lung inflammation induced by endotoxin is enhanced in rats depleted of alveolar macrophages with aerosolized clodronate. Exp Lung Res 31(6):527–46

    CAS  Article  PubMed  Google Scholar 

  72. 72.

    Maus UA, Koay MA, Delbeck T, Mack M, Ermert M, Ermert L, Blackwell TS, Christman JW, Schlondorff D, Seeger W, Lohmeyer J (2002) Role of resident alveolar macrophages in leukocyte traffic into the alveolar air space of intact mice. Am J Physiol Lung Cell Mol Physiol 282(6):L1245–52

    CAS  Article  PubMed  Google Scholar 

  73. 73.

    Koay MA, Gao X, Washington MK, Parman KS, Sadikot RT, Blackwell TS, Christman JW (2002) Macrophages are necessary for maximal nuclear factor-kappa B activation in response to endotoxin. Am J Respir Cell Mol Biol 26(5):572–8

    CAS  Article  PubMed  Google Scholar 

  74. 74.

    Martin FJ, Parker D, Harfenist BS, Soong G, Prince A (2011) Participation of CD11c(+) leukocytes in methicillin-resistant Staphylococcus aureus clearance from the lung. Infect Immun 79(5):1898–904

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  75. 75.

    Saini Y, Wilkinson KJ, Terrell KA, Burns KA, Livraghi-Butrico A, Doerschuk CM, O'Neal WK, Boucher RC (2016) Neonatal pulmonary macrophage depletion coupled to defective mucus clearance increases susceptibility to pneumonia and alters pulmonary immune responses. Am J Respir Cell Mol Biol 54(2):210–21

  76. 76.

    Roberts LM, Ledvina HE, Tuladhar S, Rana D, Steele SP, Sempowski GD, Frelinger JA (2015) Depletion of alveolar macrophages in CD11c diphtheria toxin receptor mice produces an inflammatory response. Immun Inflamm Dis 3(2):71–81

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  77. 77.

    Chapman TJ, Georas SN (2013) Adjuvant effect of diphtheria toxin after mucosal administration in both wild type and diphtheria toxin receptor engineered mouse strains. J Immunol Methods 400–401:122–6

    Article  CAS  PubMed  Google Scholar 

  78. 78.

    Bosmann M, Grailer JJ, Russkamp NF, Ruemmler R, Zetoune FS, Sarma JV, Ward PA (2013) CD11c + alveolar macrophages are a source of IL-23 during lipopolysaccharide-induced acute lung injury. Shock 39(5):447–52

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  79. 79.

    Probst HC, Tschannen K, Odermatt B, Schwendener R, Zinkernagel RM, Van Den Broek M (2005) Histological analysis of CD11c-DTR/GFP mice after in vivo depletion of dendritic cells. Clin Exp Immunol 141(3):398–404

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  80. 80.

    Lee JW, Fang X, Gupta N, Serikov V, Matthay MA (2009) Allogeneic human mesenchymal stem cells for treatment of E. coli endotoxin-induced acute lung injury in the ex vivo perfused human lung. Proc Natl Acad Sci USA 106(38):16357–62

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Acknowledgments

We are grateful to Drs. Sunita Bhattacharya, Chris Schindler, and M. Naeem Islam for their help with comments and manuscript preparation. JB was supported by NIH grants HL36024, HL57556, and HL122730.

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Correspondence to Jahar Bhattacharya.

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Bhattacharya, J., Westphalen, K. Macrophage-epithelial interactions in pulmonary alveoli. Semin Immunopathol 38, 461–469 (2016). https://doi.org/10.1007/s00281-016-0569-x

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Keywords

  • Acute Lung Injury
  • Alveolar Macrophage
  • Migration Inhibitory Factor
  • Alveolar Epithelium
  • Diphtheria Toxin