Pulmonary alveolar proteinosis, a primary immunodeficiency of impaired GM-CSF stimulation of macrophages

Current Opinion in Immunology

Volumn 21, Issue 5, 2009, Pages 514-521

  Trapnell, Bruce C ^a,b   Carey, Brenna C ^a   Uchida, Kanji ^c   Suzuki, Takuji ^a  

^a CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER   (United States)

^b UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE   (United States)

^c UNIVERSITY OF TOKYO   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOANTIBODY; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR RECEPTOR; LUNG SURFACTANT;

AUTOIMMUNE DISEASE; CATABOLISM; CELL ADHESION; CELL DIFFERENTIATION; CONGENITAL DISORDER; GENE MUTATION; HOST RESISTANCE; HUMAN; IMMUNE DEFICIENCY; INFECTION; INTRACELLULAR KILLING; LUNG ALVEOLUS MACROPHAGE; LUNG ALVEOLUS PROTEINOSIS; MACROPHAGE ACTIVATION; NEUTROPHIL; NONHUMAN; PHAGOCYTOSIS; RESPIRATORY FAILURE; REVIEW;

ANIMALS; CELL DIFFERENTIATION; GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR; HUMANS; LUNG; MACROPHAGES, ALVEOLAR; MODELS, BIOLOGICAL; PROTEIN BINDING; PULMONARY ALVEOLAR PROTEINOSIS; RECEPTORS, GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR;

EID: 70349734609     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.coi.2009.09.004     Document Type: Review

References (50)

1. Hercus T.R., Thomas D., Guthridge M.A., Ekert P.G., King-Scott J., Parker M.W., and Lopez AF. The GM-CSF receptor, linking its structure to cell signaling and its role in disease. Blood (2009). This paper presents a new model for signaling by the GM-CSF receptor, based on the recently elucidated dodecameric structure of GM-CSF bound to complexes of the GM-CSF receptor α and β chains, and Jak2. This new structure provides important new insights into the pleiotropic effects of GM-CSF derived from an understanding of the receptor's structure.
2. Trapnell B.C., and Whitsett J.A. GM-CSF regulates pulmonary surfactant homeostasis and alveolar macrophage-mediated innate host defense. Annu Rev Physiol 64 (2002) 775-802
3. Presneill J.J., Nakata K., Inoue Y., and Seymour J.F. Pulmonary alveolar proteinosis. Clin Chest Med 25 (2004) 593-613 viii
4. Trapnell B.C., Whitsett J.A., and Nakata K. Pulmonary Alveolar Proteinosis. N Engl J Med 349 (2003) 2527-2539
5. Seymour J.F., and Presneill J.J. Pulmonary alveolar proteinosis, progress in the first 44 years. Am J Respir Crit Care Med 166 (2002) 215-235. This study provides a comprehensive metaanalysis summarizing most or all of the cases of PAP reported in the medical literature from the initial description of the syndrome in 1958 through 1997.
6. Kitamura T., Tanaka N., Watanabe J., Uchida, Kanegasaki S., Yamada Y., and Nakata K. Idiopathic pulmonary alveolar proteinosis as an autoimmune disease with neutralizing antibody against granulocyte/macrophage colony-stimulating factor. J Exp Med 190 (1999) 875-880. This report was the first to identify that PAP in human individuals was associated with neutralizing GM-CSF autoantibodies.
7. Uchida K., Nakata K., Trapnell B.C., Terakawa T., Hamano E., Mikami A., Matsushita I., Seymour J.F., Oh-Eda M., Ishige I., et al. High-affinity autoantibodies specifically eliminate granulocyte-macrophage colony-stimulating factor activity in the lungs of patients with idiopathic pulmonary alveolar proteinosis. Blood 103 (2004) 1089-1098. This report demonstrated that neutralizing GM-CSF autoantibodies were highly specific for human GM-CSF, bound it with high avidity, and eliminated GM-CSF bioactivity in the lungs of PAP patients.
8. Uchida K., Nakata K., Suzuki T., Luisetti M., Watanabe M., Koch D.E., Stevens C.A., Beck D.D., Denson L.A., Carey B.C., et al. Granulocyte/macrophage colony-stimulating factor autoantibodies and myeloid cell in healthy individuals. Blood 113 (2009) 2547-2556. This report describes the critical threshold of GM-CSF autoantibody associated with an increased risk of developing PAP.
9. Bonfield T.L., Russell D., Burgess S., Malur A., Kavuru M.S., and Thomassen M.J. Autoantibodies against granulocyte macrophage colony-stimulating factor are diagnostic for pulmonary alveolar proteinosis. Am J Respir Cell Mol Biol 27 (2002) 481-486
10. Inoue Y., Trapnell B.C., Tazawa R., Arai T., Takada T., Hizawa N., Kasahara Y., Tatsumi K., Hojo M., Ichiwata T., et al. Characteristics of a large cohort of autoimmune pulmonary alveolar proteinosis patients in Japan. Am J Respir Crit Care Med 177 (2008) 752-762. This report describes the largest contemporaneous cohort of PAP patients (223 patients with autoimmune PAP) ever studied and reports on the epidemiology, clinical features, and biomarkers of autoimmune PAP.
11. Bendtzen K., Svenson M., Hansen M.B., Busch T., Bercker S., Kaisers U., Uchida K., Beck D.C., and Trapnell B.C. GM-CSF autoantibodies in pulmonary alveolar proteinosis. N Engl J Med 356 (2007) 2001-2002
12. Uchida K., Beck D.C., Yamamoto T., Berclaz P.Y., Abe S., Staudt M.K., Carey B.C., Filippi M.D., Wert S.E., Denson L.A., et al. GM-CSF autoantibodies and neutrophil dysfunction in pulmonary alveolar proteinosis. N Engl J Med 356 (2007) 567-579. This report describes the effects of highly purified GM-CSF autoantibodies on the functions of normal human neutrophils. The differential reduction in various functions of neutrophils from PAP patients and GM-CSF deficient mice was striking and suggests that GM-CSF may regulate neutrophil functions by similar mechanisms in man and mice.
13. Sakagami T., Beck D., Suzuki T., Uchida K., Wood R.E., Carey B.C., Wert S.E., Ikegami M., Whitsett J.A., Keller G., et al. Pulmonary alveolar proteinosis (PAP) reproduced in non-human primates. Am J Respir Crit Care Med 179 (2009) A3029
14. Shibata Y., Berclaz P.Y., Chroneos Z.C., Yoshida M., Whitsett J.A., and Trapnell BC. GM-CSF regulates alveolar macrophage differentiation and innate immunity in the lung through PU.1. Immunity 15 (2001) 557-567. This report demonstrated that GM-CSF must be present in the lungs to stimulate the terminal differentiation of alveolar macrophages and functions via stimulating expression of the master macrophage transcription factor, PU.1.
15. Guthridge M.A., Powell J.A., Barry E.F., Stomski F.C., McClure B.J., Ramshaw H., Felquer F.A., Dottore M., Thomas D.T., To B., et al. Growth factor pleiotropy is controlled by a receptor Tyr/Ser motif that acts as a binary switch. EMBO J 25 (2006) 479-489. The authors identified a novel motif within the β chain that is both necessary and sufficient for GM-CSF signaling, and explained how low and high GM-CSF concentrations regulate cell survival only or cell survival and proliferation.
16. Hansen G., Hercus T.R., McClure B.J., Stomski F.C., Dottore M., Powell J., Ramshaw H., Woodcock J.M., Xu Y., Guthridge M., et al. The structure of the GM-CSF receptor complex reveals a distinct mode of cytokine receptor activation. Cell 134 (2008) 496-507. This groundbreaking paper that describes the crystal structure of the GM-CSF receptor bound to its ligand revealed an unexpected, novel mechanism of signaling that is likely to be the paradigm used by other cytokine receptors.
17. Guthridge M.A., Barry E.F., Felquer F.A., McClure B.J., Stomski F.C., Ramshaw H., and Lopez A.F. The phosphoserine-585-dependent pathway of the GM-CSF/IL-3/IL-5 receptors mediates hematopoietic cell survival through activation of NF-kappaB and induction of bcl-2. Blood 103 (2004) 820-827
18. Suzuki T., Sakagami T., Rubin B.K., Nogee L.M., Wood R.E., Zimmerman S.L., Smolarek T., Dishop M.K., Wert S.E., Whitsett J.A., et al. Familial pulmonary alveolar proteinosis caused by mutations in CSF2RA. J. Exp. Med. 205 (2008) 2703-2710. This is the first report of familial PAP caused by mutations in the CSF2RA that encodes the GM-CSF receptor α chain. It demonstrated that a high serum level of GM-CSF is a biomarker of congenital PAP caused by GM-CSF receptor dysfunction.
19. Martinez-Moczygemba M., Doan M.L., Elidemir O., Fan L.L., Cheung S.W., Lei J.T., Moore J.P., Tavana G., Lewis L.R., Zhu Y., et al. Pulmonary alveolar proteinosis caused by deletion of the GM-CSFRalpha gene in the X chromosome pseudoautosomal region 1. J Exp Med 205 (2008) 2711-2716
20. Carey B.C., Suzuki T., Uchida K., Sakagami T., Wood R.E., Luisetti M., Rubin B., Kevill K., and Trapnell B.C. An algorithm for diagnosis of familial pulmonary alveolar proteinosis (PAP). Am J Respir Crit Care Med 179 (2009) A3679
21. Dirksen U., Nishinakamura R., Groneck P., Hattenhorst U., Nogee L., Murray R., and Burdach S. Human pulmonary alveolar proteinosis associated with a defect in GM-CSF/IL-3/IL-5 receptor common beta chain expression. J Clin Invest 100 (1997) 2211-2217
22. Whitsett J.A., Wert S.E., and Trapnell B.C. Genetic disorders influencing lung formation and function at birth. Hum Mol Genet 13 Spec No 2 (2004) R207-R215
23. Berclaz P.Y., Zsengeller Z., Shibata Y., Otake K., Strasbaugh S., Whitsett J.A., and Trapnell B.C. Endocytic internalization of adenovirus, nonspecific phagocytosis, and cytoskeletal organization are coordinately regulated in alveolar macrophages by GM-CSF and PU.1. J Immunol 169 (2002) 6332-6342
24. Carey B., Staudt M.K., Bonaminio D., van der Loo J.C., and Trapnell BC. PU.1 redirects adenovirus to lysosomes in alveolar macrophages. Uncoupling internalization from infection. J Immunol 178 (2007) 2440-2447
25. Yoshida M., Ikegami M., Reed J.A., Chroneos Z.C., and Whitsett J.A. GM-CSF regulates surfacant Protein-A and lipid catabolism by alveolar macrohpages. Am J Physiol Lung Cell Mol Physiol 280 (2001) L379-L386
26. Paine III R., Morris S.B., Jin H., Wilcoxen S.E., Phare S.M., Moore B.B., Coffey M.J., and Toews G.B. Impaired functional activity of alveolar macrophages from GM-CSF-deficient mice. Am J Physiol Lung Cell Mol Physiol 281 (2001) L1210-L1218
27. Berclaz P.Y., Shibata Y., Whitsett J.A., and Trapnell B.C. GM-CSF, via PU.1, regulates alveolar macrophage Fcgamma R-mediated phagocytosis and the IL-18/IFN-gamma-mediated molecular connection between innate and adaptive immunity in the lung. Blood 100 (2002) 4193-4200
28. Bonfield T.L., Raychaudhuri B., Malur A., Abraham S., Trapnell B.C., Kavuru M.S., and Thomassen M.J. PU.1 regulation of human alveolar macrophage differentiation requires granulocyte-macrophage colony-stimulating factor. Am J Physiol Lung Cell Mol Physiol 285 (2003) L1132-L1136
29. LeVine A.M., Reed J.A., Kurak K.E., Cianciolo E., and Whitsett J.A. GM-CSF-deficient mice are susceptible to pulmonary group B streptococcal infection. J Clin Invest 103 (1999) 563-569
30. Ballinger M.N., Paine III R., Serezani C.H., Aronoff D.M., Choi E.S., Standiford T.J., Toews G.B., and Moore B.B. Role of granulocyte macrophage colony-stimulating factor during gram-negative lung infection with Pseudomonas aeruginosa. Am J Respir Cell Mol Biol 34 (2006) 766-774
31. Zhan Y., Basu S., Lieschke G.J., Grail D., Dunn A.R., and Cheers C. Functional deficiencies of peritoneal cells from gene-targeted mice lacking G-CSF or GM-CSF. J Leukoc Biol 65 (1999) 256-264
32. Paine III R., Preston A.M., Wilcoxen S., Jin H., Siu B.B., Morris S.B., Reed J.A., Ross G., Whitsett J.A., and Beck J.M. Granulocyte-macrophage colony-stimulating factor in the innate immune response to Pneumocystis carinii pneumonia in mice. J Immunol 164 (2000) 2602-2609
33. Riopel J., Tam M., Mohan K., Marino M.W., and Stevenson M.M. Granulocyte-macrophage colony-stimulating factor-deficient mice have impaired resistance to blood-stage malaria. Infect Immun 69 (2001) 129-136
34. Gonzalez-Juarrero M., Hattle J.M., Izzo A., Junqueira-Kipnis A.P., Shim T.S., Trapnell B.C., Cooper A.M., and Orme I.M. Disruption of granulocyte macrophage-colony stimulating factor production in the lungs severely affects the ability of mice to control Mycobacterium tuberculosis infection. J Leukoc Biol 77 (2005) 914-922
35. Spight D., Trapnell B., Zhao B., Berclaz P., and Shanley T.P. Granulocyte-macrophage-colony-stimulating factor-dependent peritoneal macrophage responses determine survival in experimentally induced peritonitis and sepsis in mice. Shock 30 (2008) 434-442
36. Moore B.B., Coffey M.J., Christensen P., Sitterding S., Ngan R., Wilke C.A., McDonald R., Phare S.M., Peters-Golden M., Paine III R., et al. GM-CSF regulates bleomycin-induced pulmonary fibrosis via a prostaglandin-dependent mechanism. J Immunol 165 (2000) 4032-4039
37. Berclaz P.Y., Carey B., Fillipi M.D., Wernke-Dollries K., Geraci N., Cush S., Richardson T., Kitzmiller J., O'Connor M., Hermoyian C., et al. GM-CSF regulates a PU.1-dependent transcriptional program determining the pulmonary response to LPS. Am J Respir Cell Mol Biol 36 (2007) 114-121
38. Bozinovski S., Jones J., Beavitt S.J., Cook A.D., Hamilton J.A., and Anderson G.P. Innate immune responses to LPS in mouse lung are suppressed and reversed by neutralization of GM-CSF via repression of TLR-4. Am J Physiol Lung Cell Mol Physiol 286 (2004) L877-L885. This report demonstrated that administration of neutralizing GM-CSF autoantibodies modulates inflammatory host responses in a rheostatic fashion in mice. This provided data supporting the feasibility of using GM-CSF autoantibodies therapeutically in serious inflammatory and autoimmune diseases.
39. Fleetwood A.J., Cook A.D., and Hamilton J.A. Functions of granulocyte-macrophage colony-stimulating factor. Crit Rev Immunol 25 (2005) 405-428
40. Hamilton J.A. Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol 8 (2008) 533-544. This paper provides an excellent review of the role of GM-CSF autoimmune disorders and of clinical trials aimed at evaluating the use of neutralizing GM-CSF autoantibodies to treat serious inflammatory and autoimmune diseases.
41. Campbell I.K., Bendele A., Smith D.A., and Hamilton J.A. Granulocyte-macrophage colony stimulating factor exacerbates collagen induced arthritis in mice. Ann Rheum Dis 56 (1997) 364-368
42. Xu W.D., Firestein G.S., Taetle R., Kaushansky K., and Zvaifler N.J. Cytokines in chronic inflammatory arthritis. II. Granulocyte-macrophage colony-stimulating factor in rheumatoid synovial effusions. J Clin Invest 83 (1989) 876-882
43. McQualter J.L., Darwiche R., Ewing C., Onuki M., Kay T.W., Hamilton J.A., Reid H.H., and Bernard C.C. Granulocyte macrophage colony-stimulating factor, a new putative therapeutic target in multiple sclerosis. J Exp Med 194 (2001) 873-882. This study implicated GM-CSF in experimental allergic encephalitis, suggesting a potential therapeutic application of neutralizing GM-CSF autoantibodies to treat individuals with multiple sclerosis.
44. Kitching A.R., Ru Huang X., Turner A.L., Tipping P.G., Dunn A.R., and Holdsworth S.R. The requirement for granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in leukocyte-mediated immune glomerular injury. J Am Soc Nephrol 13 (2002) 350-358
45. Alderuccio F., Biondo M., and Toh B.H. Organ-specific autoimmunity in granulocyte macrophage-colony stimulating factor (GM-CSF) deficient mice. Autoimmunity 35 (2002) 67-73
46. Frossard J.L., Saluja A.K., Mach N., Lee H.S., Bhagat L., Hadenque A., Rubbia-Brandt L., Dranoff G., and Steer M.L. In vivo evidence for the role of GM-CSF as a mediator in acute pancreatitis-associated lung injury. Am J Physiol Lung Cell Mol Physiol 283 (2002) L541-L548
47. Iyonaga K., Suga M., Yamamoto T., Ichiyasu H., Miyakawa H., and Ando M. Elevated bronchoalveolar concentrations of MCP-1 in patients with pulmonary alveolar proteinosis. Eur Respir J 14 (1999) 383-389
48. Golde D.W., Territo M., Finley T.N., and Cline M.J. Defective lung macrophages in pulmonary alveolar proteinosis. Ann Intern Med 85 (1976) 304-309
49. Tazawa R., Hamano E., Arai T., Ohta H., Ishimoto O., Uchida K., Watanabe M., Saito J., Takeshita M., Hirabayashi Y., et al. Granulocyte-macrophage colony-stimulating factor and lung immunity in pulmonary alveolar proteinosis. Am J Respir Crit Care Med 171 (2005) 1142-1149
50. Dranoff G., Crawford A.D., Sadelain M., Ream B., Rashid A., Bronson R.T., Dickersin G.R., Bachurski C.J., Mark E.L., Whitsett J.A., et al. Involvement of granulocyte-macrophage colony-stimulating factor in pulmonary homeostasis. Science 264 (1994) 713-716. This groundbreaking report identified the crucial role of GM-CSF in surfactant homeostasis and alveolar macrophage function.