Modification of Hemodynamic and Immune Responses to Exposure with a Weak Antigen by the Expression of a Hypomorphic BMPR2 Gene

PLoS ONE

Volumn 8, Issue 1, 2013, Pages

  Park, Sung Hyun ^a   Chen, Wen Chi ^a   Hoffman, Carol ^a   Marsh, Leigh M ^b   West, James ^c   Grunig, Gabriele ^a  

^a NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b LUDWIG BOLTZMANN INSTITUTE FOR LUNG VASCULAR RESEARCH   (Austria)

^c VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BONE MORPHOGENETIC PROTEIN RECEPTOR 2; GAMMA INTERFERON; INTERLEUKIN 1 RECEPTOR; INTERLEUKIN 13; INTERLEUKIN 33; OVALBUMIN; RESISTIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BMPR2 GENE; CONTROLLED STUDY; FEMALE; GENE EXPRESSION; HEART RIGHT VENTRICLE PRESSURE; HEMODYNAMICS; IMMUNE FUNCTION TEST; IMMUNE RESPONSE; MOUSE; NONHUMAN; PROTEIN EXPRESSION; PULMONARY ARTERY; PULMONARY HYPERTENSION; RESPIRATORY TRACT INFLAMMATION; SYSTOLIC BLOOD PRESSURE; T LYMPHOCYTE; TRANSGENE;

ANIMALS; ANTIGENS; BLOOD PRESSURE; BODY WEIGHT; BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE II; BRONCHOALVEOLAR LAVAGE; DNA PRIMERS; HEART VENTRICLES; HEMODYNAMICS; HYPERTENSION, PULMONARY; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; INTERLEUKINS; MICE; MICE, TRANSGENIC; ORGAN SIZE; OVALBUMIN; RECEPTORS, INTERLEUKIN; TH2 CELLS; TRANSGENES;

EID: 84873873522     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0055180     Document Type: Article

References (63)

1. Zaiman A, Fijalkowska I, Hassoun PM, Tuder RM, (2005) One hundred years of research in the pathogenesis of pulmonary hypertension. Am J Respir Cell Mol Biol 33: 425-431.
2. West J, (2010) Cross talk between Smad, MAPK, and actin in the etiology of pulmonary arterial hypertension. Adv Exp Med Biol 661: 265-278.
3. Daley E, Emson C, Guignabert C, de Waal Malefyt R, Louten J, et al. (2008) Pulmonary arterial remodeling induced by a Th2 immune response. J Exp Med 205: 361-372.
4. Gilboa L, Nohe A, Geissendorfer T, Sebald W, Henis YI, et al. (2000) Bone morphogenetic protein receptor complexes on the surface of live cells: a new oligomerization mode for serine/threonine kinase receptors. Mol Biol Cell 11: 1023-1035.
5. Phillips JA 3rd, Poling JS, Phillips CA, Stanton KC, Austin ED, et al. (2008) Synergistic heterozygosity for TGFbeta1 SNPs and BMPR2 mutations modulates the age at diagnosis and penetrance of familial pulmonary arterial hypertension. Genet Med 10: 359-365.
6. Eickelberg O, Morty RE, (2007) Transforming growth factor beta/bone morphogenic protein signaling in pulmonary arterial hypertension: remodeling revisited. Trends Cardiovasc Med 17: 263-269.
7. Upton PD, Morrell NW, (2009) TGF-beta and BMPR-II pharmacology-implications for pulmonary vascular diseases. Curr Opin Pharmacol 9: 274-280.
8. Davies RJ, Holmes AM, Deighton J, Long L, Yang X, et al. (2012) BMP type II receptor deficiency confers resistance to growth inhibition by TGF-beta in pulmonary artery smooth muscle cells: role of proinflammatory cytokines. Am J Physiol Lung Cell Mol Physiol 302: L604-615.
9. Morrell NW, Yang X, Upton PD, Jourdan KB, Morgan N, et al. (2001) Altered growth responses of pulmonary artery smooth muscle cells from patients with primary pulmonary hypertension to transforming growth factor-beta(1) and bone morphogenetic proteins. Circulation 104: 790-795.
10. Deng Z, Morse JH, Slager SL, Cuervo N, Moore KJ, et al. (2000) Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene. Am J Hum Genet 67: 737-744.
11. Newman JH, Wheeler L, Lane KB, Loyd E, Gaddipati R, et al. (2001) Mutation in the gene for bone morphogenetic protein receptor II as a cause of primary pulmonary hypertension in a large kindred. N Engl J Med 345: 319-324.
12. Lane KB, Machado RD, Pauciulo MW, Thomson JR, Phillips JA 3rd, et al. (2000) Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. The International PPH Consortium. Nat Genet 26: 81-84.
13. Machado RD, Pauciulo MW, Thomson JR, Lane KB, Morgan NV, et al. (2001) BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension. Am J Hum Genet 68: 92-102.
14. Newman JH, Trembath RC, Morse JA, Grunig E, Loyd JE, et al. (2004) Genetic basis of pulmonary arterial hypertension: current understanding and future directions. J Am Coll Cardiol 43: 33S-39S.
15. Rabinovitch M, (2008) Molecular pathogenesis of pulmonary arterial hypertension. J Clin Invest 118: 2372-2379.
16. Austin ED, Hamid R, Hemnes AR, Loyd JE, Blackwell T, et al. (2012) BMPR2 expression is suppressed by signaling through the estrogen receptor. Biol Sex Differ 3: 6.
17. West J, Cogan J, Geraci M, Robinson L, Newman J, et al. (2008) Gene expression in BMPR2 mutation carriers with and without evidence of Pulmonary Arterial Hypertension suggests pathways relevant to disease penetrance. BMC Med Genomics 1: 45.
18. Mushaben EM, Hershey GK, Pauciulo MW, Nichols WC, Le Cras TD, (2012) Chronic allergic inflammation causes vascular remodeling and pulmonary hypertension in BMPR2 hypomorph and wild-type mice. PLoS One 7: e32468.
19. Price LC, Wort SJ, Perros F, Dorfmuller P, Huertas A, et al. (2012) Inflammation in pulmonary arterial hypertension. Chest 141: 210-221.
20. Perros F, Dorfmuller P, Humbert M, (2005) Current insights on the pathogenesis of pulmonary arterial hypertension. Semin Respir Crit Care Med 26: 355-364.
21. Song Y, Coleman L, Shi J, Beppu H, Sato K, et al. (2008) Inflammation, endothelial injury, and persistent pulmonary hypertension in heterozygous BMPR2-mutant mice. Am J Physiol Heart Circ Physiol 295: H677-690.
22. West J, Harral J, Lane K, Deng Y, Ickes B, et al. (2008) Mice expressing BMPR2R899X transgene in smooth muscle develop pulmonary vascular lesions. Am J Physiol Lung Cell Mol Physiol 295: L744-755.
23. Talati M, West J, Blackwell TR, Loyd JE, Meyrick B, (2010) BMPR2 mutation alters the lung macrophage endothelin-1 cascade in a mouse model and patients with heritable pulmonary artery hypertension. Am J Physiol Lung Cell Mol Physiol 299: L363-373.
24. Johnson JA, Hemnes AR, Perrien DS, Schuster M, Robinson LJ, et al. (2012) Cytoskeletal defects in Bmpr2-associated pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol 302: L474-484.
25. Schermuly RT, Dony E, Ghofrani HA, Pullamsetti S, Savai R, et al. (2005) Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest 115: 2811-2821.
26. Crnkovic S, Hrzenjak A, Marsh LM, Olschewski A, Kwapiszewska G, (2011) Origin of neomuscularized vessels in mice exposed to chronic hypoxia. Respir Physiol Neurobiol 179: 342-345.
27. Hoffman C, Park SH, Daley E, Emson C, Louten J, et al. (2011) Interleukin-19: a constituent of the regulome that controls antigen presenting cells in the lungs and airway responses to microbial products. PLoS One 6: e27629.
28. Padilla J, Daley E, Chow A, Robinson K, Parthasarathi K, et al. (2005) IL-13 Regulates the Immune Response to Inhaled Antigens. J Immunol 174: 8097-8105.
29. Ford JG, Rennick D, Donaldson DD, Venkayya R, McArthur C, et al. (2001) IL-13 and IFN-gamma: interactions in lung inflammation. J Immunol 167: 1769-1777.
30. Grunig G, Warnock M, Wakil AE, Venkayya R, Brombacher F, et al. (1998) Requirement for IL-13 Independently of IL-4 in Experimental Asthma. Science 282: 2261-2263.
31. Gottschalk RA, Corse E, Allison JP, (2012) Expression of Helios in peripherally induced Foxp3+ regulatory T cells. J Immunol 188: 976-980.
32. Thornton AM, Korty PE, Tran DQ, Wohlfert EA, Murray PE, et al. (2010) Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J Immunol 184: 3433-3441.
33. Serre K, Benezech C, Desanti G, Bobat S, Toellner KM, et al. (2011) Helios is associated with CD4 T cells differentiating to T helper 2 and follicular helper T cells in vivo independently of Foxp3 expression. PLoS One 6: e20731.
34. Hassoun PM, Mouthon L, Barbera JA, Eddahibi S, Flores SC, et al. (2009) Inflammation, growth factors, and pulmonary vascular remodeling. J Am Coll Cardiol 54: S10-19.
35. Perros F, Dorfmuller P, Montani D, Hammad H, Waelput W, et al. (2012) Pulmonary lymphoid neogenesis in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 185: 311-321.
36. Said SI, Hamidi SA, Gonzalez Bosc L, (2010) Asthma and pulmonary arterial hypertension: do they share a key mechanism of pathogenesis? Eur Respir J 35: 730-734.
37. Soon E, Holmes AM, Treacy CM, Doughty NJ, Southgate L, et al. (2010) Elevated levels of inflammatory cytokines predict survival in idiopathic and familial pulmonary arterial hypertension. Circulation 122: 920-927.
38. Tamosiuniene R, Tian W, Dhillon G, Wang L, Sung YK, et al. (2011) Regulatory T cells limit vascular endothelial injury and prevent pulmonary hypertension. Circ Res 109: 867-879.
39. Hoffmann J, Yin J, Kukucka M, Yin N, Saarikko I, et al. (2011) Mast cells promote lung vascular remodelling in pulmonary hypertension. Eur Respir J 37: 1400-1410.
40. Liu D, Liu QQ, Eyries M, Wu WH, Yuan P, et al. (2012) Molecular genetics and clinical features of Chinese idiopathic and heritable pulmonary arterial hypertension patients. Eur Respir J 39: 597-603.
41. Girerd B, Montani D, Eyries M, Yaici A, Sztrymf B, et al. (2010) Absence of influence of gender and BMPR2 mutation type on clinical phenotypes of pulmonary arterial hypertension. Respir Res 11: 73.
42. Sztrymf B, Coulet F, Girerd B, Yaici A, Jais X, et al. (2008) Clinical outcomes of pulmonary arterial hypertension in carriers of BMPR2 mutation. Am J Respir Crit Care Med 177: 1377-1383.
43. Pfarr N, Szamalek-Hoegel J, Fischer C, Hinderhofer K, Nagel C, et al. (2011) Hemodynamic and clinical onset in patients with hereditary pulmonary arterial hypertension and BMPR2 mutations. Respir Res 12: 99.
44. Rosenzweig EB, Morse JH, Knowles JA, Chada KK, Khan AM, et al. (2008) Clinical implications of determining BMPR2 mutation status in a large cohort of children and adults with pulmonary arterial hypertension. J Heart Lung Transplant 27: 668-674.
45. Louten J, Rankin AL, Li Y, Murphy EE, Beaumont M, et al. (2011) Endogenous IL-33 enhances Th2 cytokine production and T-cell responses during allergic airway inflammation. Int Immunol 23: 307-315.
46. Kurowska-Stolarska M, Kewin P, Murphy G, Russo RC, Stolarski B, et al. (2008) IL-33 induces antigen-specific IL-5+ T cells and promotes allergic-induced airway inflammation independent of IL-4. J Immunol 181: 4780-4790.
47. Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, et al. (2005) IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 23: 479-490.
48. Munitz A, Cole ET, Karo-Atar D, Finkelman FD, Rothenberg ME, (2012) Resistin-like molecule-alpha regulates IL-13-induced chemokine production but not allergen-induced airway responses. Am J Respir Cell Mol Biol 46: 703-713.
49. Munitz A, Waddell A, Seidu L, Cole ET, Ahrens R, et al. (2008) Resistin-like molecule alpha enhances myeloid cell activation and promotes colitis. J Allergy Clin Immunol 122: 1200-1207 e1201.
50. Wills-Karp M, Luyimbazi J, Xu X, Schofield B, Neben TY, et al. (1998) Interleukin-13: central mediator of allergic asthma. Science 282: 2258-2261.
51. Baum JR, Long B, Cabo C, Duffy HS, (2012) Myofibroblasts cause heterogeneous Cx43 reduction and are unlikely to be coupled to myocytes in the healing canine infarct. Am J Physiol Heart Circ Physiol 302: H790-800.
52. Ma F, Li Y, Jia L, Han Y, Cheng J, et al. (2012) Macrophage-stimulated cardiac fibroblast production of IL-6 is essential for TGF beta/Smad activation and cardiac fibrosis induced by angiotensin II. PLoS One 7: e35144.
53. Kakkar R, Lee RT, (2008) The IL-33/ST2 pathway: therapeutic target and novel biomarker. Nat Rev Drug Discov 7: 827-840.
54. Sanada S, Hakuno D, Higgins LJ, Schreiter ER, McKenzie AN, et al. (2007) IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system. J Clin Invest 117: 1538-1549.
55. Angelini DJ, Su Q, Yamaji-Kegan K, Fan C, Skinner JT, et al. (2009) Hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMalpha) induces the vascular and hemodynamic changes of pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 296: L582-593.
56. Nair MG, Du Y, Perrigoue JG, Zaph C, Taylor JJ, et al. (2009) Alternatively activated macrophage-derived RELM-{alpha} is a negative regulator of type 2 inflammation in the lung. J Exp Med 206: 937-952.
57. Pesce JT, Ramalingam TR, Wilson MS, Mentink-Kane MM, Thompson RW, et al. (2009) Retnla (relmalpha/fizz1) suppresses helminth-induced th2-type immunity. PLoS Pathog 5: e1000393.
58. Li MO, Wan YY, Sanjabi S, Robertson AKL, Flavell RA, (2006) Transforming growth factor-beta regulation of immune responses. Annual Review of Immunology 24: 99-146.
59. Reynolds LA, Maizels RM, (2012) Cutting Edge: In the Absence of TGF-beta Signaling in T Cells, Fewer CD103(+) Regulatory T Cells Develop, but Exuberant IFN-gamma Production Renders Mice More Susceptible to Helminth Infection. Journal of Immunology 189: 1113-1117.
60. Hager-Theodorides AL, Outram SV, Shah DK, Sacedon R, Shrimpton RE, et al. (2002) Bone morphogenetic protein 2/4 signaling regulates early thymocyte differentiation. J Immunol 169: 5496-5504.
61. Rastogi D, Ngai P, Barst RJ, Koumbourlis AC, (2004) Lower airway obstruction, bronchial hyperresponsiveness, and primary pulmonary hypertension in children. Pediatr Pulmonol 37: 50-55.
62. Chen WC, Park SH, Hoffman C, Philip C, Robinson L, et al. (2012) Right ventricular systolic pressure measurements in combination with harvest of lung and immune tissue samples in mice. J Visualized Experiments in press.
63. Grunig G, Corry DB, Leach MW, Seymour BW, Kurup VP, et al. (1997) Interleukin-10 is a natural suppressor of cytokine production and inflammation in a murine model of allergic bronchopulmonary aspergillosis. J Exp Med 185: 1089-1099.