European Archives of Oto-Rhino-Laryngology

, Volume 252, Supplement 1, pp S50–S58 | Cite as

Implicating adhesion molecules in nasal allergic inflammation

  • F. M. Baroody
  • B. -J. Lee
  • M. C. Lim
  • B. S. Bochner
Review Article


Allergic rhinitis is now considered an inflammatory disorder where many leukocyte types, including eosinophils and T-lymphocytes, accumulate in increased numbers. Along with mast cells and other cells, they release a wide variety of mediators, cytokines, and granule constituents that can directly cause inflammation or activate the local vascular endothelium to futher enhance the recruitment of leukocytes through the expression and function of adhesion molecules. While the understanding of the importance of leukocyte and endothelial adhesion molecules is still at a very early stage, recent evidence has already begun to implicate these cell surface molecules in the pathogenesis of allergic diseases such as rhinitis and asthma. Additional studies, including the use of adhesion molecule antagonists when available, will clarify the importance of these structures in the pathophysiology of these disorders.

Key words

Allergic rhinitis Pathophysiology Adhesion molecules Eosinophils Mast cells 


  1. 1.
    Alam R, Sim TC, Hilsmeier K, Grant JA (1992) Development of a new technique for recovery of cytokines from inflammatory sites in situ. J Immunol Methods 155:25–29PubMedCrossRefGoogle Scholar
  2. 2.
    Alam R, Stafford S, Forsythe P, Harrison R, Faubion D, Lett-Brown M, Grant J (1993) RANTES is a chemotactic and activating factor for human eosinophils. J Immunol 150:3442–3447PubMedGoogle Scholar
  3. 3.
    Albelda SM, Buck CA (1990) Integrins and other cell adhesion molecules. FASEB J 4:2868–2880PubMedGoogle Scholar
  4. 4.
    Anderson DC, Schmalstieg FC, Finegold MJ, Hughes BJ, Rothlein R, Miller LJ, Kohl S, Tosi MF, Jacobs RL, Waldrop TC, Goldman AS, Shearer WT, Springer TA (1985) The severe and moderate phenotypes of heritable Mac-1, LFA-1, p150,95 deficiency: their quantitative definition and relation to leukocyte dysfunction and clinical features. J Infect Dis 152:668–689PubMedGoogle Scholar
  5. 5.
    Bascom R, Pipkorn U, Proud D, Dunnette S, Gleich GJ, Lichtenstein LM, Naclerio RM (1989) Major basic protein and eosinophil-derived neurotoxin concentrations in nasal-lavage fluid after antigen challenge: effect of systemic corticosteroids and relationship to eosinophil influx. J Allergy Clin Immunol 84:338–346PubMedCrossRefGoogle Scholar
  6. 6.
    Bascom R, Wachs M, Naclerio RM, Pipkorn U, Galli SJ, Lichtenstein LM (1988) Basophil influx occurs after nasal antigen challenge: effects of topical corticosteroid pretreatment. J Allergy Clin Immunol 81:580–589PubMedCrossRefGoogle Scholar
  7. 7.
    Benenati S, Bochner B, Horn T, Farmer E, Schleimer R (1991) Endothelial-leukocyte adhesion molecule-1 (SLAM-1) expression following cutaneous allergen challenge (abstract). J Allergy Clin Immunol 87:304CrossRefGoogle Scholar
  8. 8.
    Bentley A, Jacobson M, Cumberworth V, Barkans J, Moqbel R, Schwartz L, Irani A, Kay A, Durham S (1992) Immunohistology of the nasal mucosa in seasonal allergic rhinitis: increase in activated eosinophils and epithelial mast cells. J Allergy Clin Immunol 89:877–883PubMedCrossRefGoogle Scholar
  9. 9.
    Bevilacqua MP, Nelson RM (1993) Selectins. J Clin Invest 91:379–387PubMedGoogle Scholar
  10. 10.
    Bevilacqua MP, Pober JS, Wheeler ME, Cotran RS, Gimbrone MA Jr (1985) Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocytic cell lines. J Clin Invest 76:2003–2011PubMedGoogle Scholar
  11. 11.
    Bochner BS, Luscinskas FW, Gimbrone MA Jr, Newman W, Sterbinsky SA, Derse-Anthony C, Klunk D, Schleimer RP (1991) Adhesion of human basophils, eosinophils, and neutrophils to IL-1-activated human vascular endothelial cells: contributions of endothelial cell adhesion molecules. J Exp Med 173:1553–1557PubMedCrossRefGoogle Scholar
  12. 12.
    Bochner BS, Peachell PT, Brown KE, Schleimer RP (1988) Adherence of human basophils to cultured umbilical vein vascular endothelial cells. J Clin Invest 81:1355–1360PubMedGoogle Scholar
  13. 13.
    Bochner BS, Sterbinsky SA, Bickel CA, Werfel S, Wein M, Newman W (1994) Differences between human eosinophils and neutrophils in the function and expression of sialic acidcontaining counterligands for E-selectin. J Immunol 152:774–782PubMedGoogle Scholar
  14. 14.
    Bradding P, Feather IH, Howarth PH, Mueller R, Roberts JA, Britten K, Bews JPA, Hunt TC, Okayama Y, Heusser CH, Bullock GR, Church MK, Holgate ST (1992) Interleukin-4 is localized to and released by human mast cells. J Exp Med 176:1381–1386PubMedCrossRefGoogle Scholar
  15. 15.
    Butcher EC (1991) Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell 67:1033–1036PubMedCrossRefGoogle Scholar
  16. 16.
    Creticos PS, Peters SP, Adkinson NF Jr, Naclerio RM, Hayes EC, Norman PS, Lichtenstein LM (1984) Peptide leukotriene release after antigen challenge in patients sensitive to ragweed. N Engl J Med 310:1626–1630PubMedCrossRefGoogle Scholar
  17. 17.
    Dobrina A, Menegazzi R, Carlos TM, Nardon E, Cramer R, Zacchi T, Harlan JM, Patriarca P (1991) Mechanisms of eosinophil adherence to cultured vascular endothelial cells: eosinophils bind to the cytokine-induced endothelial ligand vascular cell adhesion molecule-1 via the very late activation antigen-4 integrin receptor. J Clin Invest 88:20–26PubMedGoogle Scholar
  18. 18.
    Durham SR, Ying S, Varney VA, Jacobson MR, Sudderick RM, Mackay IS, Kay AB, Hamid QA (1992) Cytokine messenger RNA expression for IL-3, IL-4, IL-5, and gianulocytemacrophage colony-stimulating factor in the nasal mucosa after local allergen provocation — relationship to tissue eosinophilia. J Immunol 148:2390–2394PubMedGoogle Scholar
  19. 19.
    Dvoracek JE, Yunginger JW, Kern EB, Hyatt RE, Gleich EJ (1984) Induction of nasal late-phase reactions by insufflation of ragweed-pollen extract. J Allergy Clin Immunol 73:363–368PubMedCrossRefGoogle Scholar
  20. 20.
    Ebisawa M, Bochner BS, Georas SN, Schleimer RP (1992) Eosinophil transendothelial migration induced by cytokines. I. Role of endothelial and eosinophil adhesion molecules in IL-1β-induced transendothelial migration. J Immunol 149:4021–4028PubMedGoogle Scholar
  21. 21.
    Ebisawa M, Liu MC, Yamada T, Kato M, Lichtenstein LM, Bochner BS, Schleimer RP (1994) Eosinophil transendothelial migration induced by cytokines. II. The potentiation of eosinophil transendothelial migration by eosinophil-active cytokines. J Immunol 152:4590–4597PubMedGoogle Scholar
  22. 22.
    Ebisawa M, Yamada T, Klunk D, Bickel C, Liu M, Bochner BS, Schleimer RP (1993) Regulation of eosinophil and neutrophil transendothelial migration by cytokines and chemokines (abstract). J Allergy Clin Immunol 91:691Google Scholar
  23. 23.
    Georas SN, Liu MC, Newman W, Beall WD, Stealey BA, Bochner BS (1992) Altered adhesion molecule expression and endothelial activation accompany the recruitment of human granulocytes to the lung following segmental antigen challenge. Am J Respir Cell Mol Biol 7:261–269PubMedGoogle Scholar
  24. 24.
    Gomes E, Corrado OJ, Baldwin DL, Swanston AR, Davies RJ (1986) Direct in vivo evidence for mast cell degranulation during allergen-induced reactions in man. J Allergy Clin Immunol 78:637–645CrossRefGoogle Scholar
  25. 25.
    Gundel RH, Wegner CD, Torcellini CA, Clarke CC, Haynes N, Rothlein R, Smith CW, Letts LG (1991) Endothelial leukocyte adhesion molecule-1 mediates antigen-induced acute airway inflammation and late-phase airway obstruction in monkeys. J Clin Invest 88:1407–1411PubMedGoogle Scholar
  26. 26.
    Hamid Q, Barkans J, Robinson D, Durham S, Kay A (1992) Co-expression of CD25 and CD3 in atopic allergy and asthma. Immunology 75:659–663PubMedGoogle Scholar
  27. 27.
    Hansel TT, Walker C (1992) The migration of eosinophils into the sputum of asthmatics: the role of adhesion molecules. Clin Exp Allergy 22:345–356PubMedCrossRefGoogle Scholar
  28. 28.
    Hastie R, Chir B, Heroy JH, Levy DA (1979) Basophil leukocytes and mast cells in human nasal secretions and scrapings studied by light microscopy. Lab Invest 40:554–561PubMedGoogle Scholar
  29. 29.
    Hemler ME (1990) VLA proteins in the integrin family: structures, functions, and their role on leukocytes. Annu Rev Immunol 8:365–400PubMedCrossRefGoogle Scholar
  30. 30.
    Huber AR, Kunkel SL, Todd RF III, Weiss SJ (1991) Regulation of transendothelial neutrophil migration by endogenous interleukin-8. Science 254:99–102PubMedGoogle Scholar
  31. 31.
    Iliopoulos O, Baroody FM, Naclerio RM, Bochner BS, Kagey-Sobotka A, Lichtenstein LM (1992) Histamine containing cells obtained from the nose hours after antigen challenge have functional and phenotypic characteristics of basophils J Immunol 148:2223–2228PubMedGoogle Scholar
  32. 32.
    Kaiser J, Bickel C, Bochner BS, Schleimer RP (1993) The effects of the potent glucocorticoid budesonide on adhesion of eosinophils to human vascular endothelium and on endothelial expression of adhesion molecules. J Pharmacol Exp Therap 245–249Google Scholar
  33. 33.
    Kaliner M, Lemanske R (1992) Rhinitis and asthma. JAMA 268:2807–2829PubMedCrossRefGoogle Scholar
  34. 34.
    Kameyoshi Y, Dorschner A, Mallet AI, Christophers E, Schroder JM (1992) Cytokine RANTES released by thrombinstimulated platelets is a potent attractant for human eosinophils. J Exp Med 176:587–592PubMedCrossRefGoogle Scholar
  35. 35.
    Kay AB, Ying S, Varney SR, Gaga M, Durham SR, Moqbel R, Wardlaw AJ, Hamid Q (1991) Messenger RNA expression of the cytokine gene cluster, interleukin-3 (IL-3), IL-4, IL-5, and granulocyte/macrophage colony-stimulating factor, in allergeninduced late-phase cutaneous reactions in atopic subjects. J Exp Med 173:775–778PubMedCrossRefGoogle Scholar
  36. 36.
    Knol EF, Tackey F, Tedder TF, Klunk DA, Bickel C, Sterbinsky SA, Bochner BS (1994) Comparison of human eosinophil and neutrophil adhesion to endothelial cells under non-static conditions: the role of L-selectin. J Immunol 153:2161–2167PubMedGoogle Scholar
  37. 37.
    Kroegel C, Liu MC, Hubbard WM, Lichtenstein LM, Bochner BS (1994) Blood and bronchoalveolar eosinophils in allergic subjects following segmental antigen challenge: surface phenotype, density heterogeneity, and prostanoid production. J Allergy Clin Immunol 93:725–734PubMedCrossRefGoogle Scholar
  38. 38.
    Kuijpers TW, Mul EPJ, Blom M, Kovach NL, Gaeta FCA, Tollefson V, Elices MJ, Harlan JM (1993) Freezing adhesion molecules in a state of high-avidity binding blocks eosinophil migration. J Exp Med 178:279–284PubMedCrossRefGoogle Scholar
  39. 39.
    Kyan-Aung U, Haskard DO, Poston RN, Thornhill MH, Lee TH (1991) Endothelial leukocyte adhesion molecule-1 and intercellular adhesion molecule-1 mediate the adhesion of eosinophils to endothelial cells in vitro and are expressed by endothelium in allergic cutaneous inflammation in vivo. J Immunol 146:521–528PubMedGoogle Scholar
  40. 40.
    Lamas AM, Mulroney CR, Schleimer RP (1988) Studies on the adhesive interaction between human eosinophils and cultured vascular endothelial cells. J Immunol 140:1500–1505PubMedGoogle Scholar
  41. 41.
    Lee B-J, Naclerio RM, Bochner BS, Taylor RM, Lim MC, Baroody FM (1994) Nasal challenge with allergen upregulates the local expression of vascular endothelial adhesion molecules. J Allergy Clin Immunol (in press)Google Scholar
  42. 42.
    Leung DYM, Pober JS, Cotran RS (1991) Expression of endothelial-leukocyte adhesion molecule-1 in elicited late phase allergic reactions. J Clin Invest 87:1805–1809PubMedGoogle Scholar
  43. 43.
    Lim-Mombay M, Baroody F, Taylor R, Naclerio R (1992) Mucosal cellular changes after nasal antigen challenge (abstract). J Allergy Clin Immunol 89:205Google Scholar
  44. 44.
    Lo SK, Lee S, Ramos RA, Lobb R, Rosa M, Chirosso G, Wright SD (1991) Endothelial-leukocyte adhesion molecule-1 stimulates the adhesive activity of leukocyte integrin CR3 (CD11b/CD18, Mac-1, αmβ2) on human neutrophils. J Exp Med 173:1493–1500PubMedCrossRefGoogle Scholar
  45. 45.
    Luscinskas FW, Cybulsky MI, Kiely J-M, Peckins CS, Davis VM, Gimbrone MA Jr (1991) Cytokine-activated human endothelial monolayers support enhanced neutrophil transmigration via a mechanism involving both endothelial-leukocyte adhesion molecule-1 and intracellular adhesion molecule-1. J Immunol 146:1617–1625PubMedGoogle Scholar
  46. 46.
    Mengelers HJJ, Maikoe T, Hooibrink B, Kuypers TW, Kreukniet J, Lammers J-WJ, Koenderman L (1993) Down modulation of L-selectin expression on eosinophils recovered from bronchoalveolar lavage fluid after allergen provocation. Clin Exp Allergy 23:196–204PubMedCrossRefGoogle Scholar
  47. 47.
    Montefort S, Feather IH, Wilson SJ, Haskard DO, Lee TH, Holgate ST, Howarth PH (1992) The expression of leukocyteendothelial adhesion molecules is increased in perennial allergic rhinitits. Am J Respir Cell Mol Biol 7:393–398PubMedGoogle Scholar
  48. 48.
    Montefort S, Roche WR, Howarth PH, Djukanovic R, Gratziou C, Carroll M, Smith L, Britten KM, Haskard D, Lee TH, Holgate ST (1992) Intercellular adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1) expression in the bronchial mucosa of normal and asthmatic subjects. Eur Respir J 5:815–823PubMedGoogle Scholar
  49. 49.
    Moser R, Fehr J, Olgiati L, Bruijnzeel PL (1992) Migration of primed human eosinophils across cytokine-activated endothelial cell monolayers. Blood 79:2937–2945PubMedGoogle Scholar
  50. 50.
    Moser R, Schleiffenbaum B, Groscurth P, Fehr J (1989) Interleukin 1 and tumor necrosis factor stimulate human vascular endothelial cells to promote transendothelial neutrophil passage. J Clin Invest 83:444–455PubMedCrossRefGoogle Scholar
  51. 51.
    Mosmann TR, Coffman RL (1989) TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Ann Rev Immunol 7:145–173CrossRefGoogle Scholar
  52. 52.
    Naclerio RM, Meier HC, Kagey-Sobotka A, Adkinson NF Jr, Meyers DA, Norman PS, Lichtenstein LM (1983) Mediator release after nasal airway challenge with allergen. Am Rev Respir Dis 128:597–602PubMedGoogle Scholar
  53. 53.
    Naclerio RM, Proud D, Togias AG, Adkinson NF Jr, Meyers DA, Kagey-Sobotka A, Plant M, Norman PS, Lichtenstein LM (1985) Inflammatroy mediators in late antigen-induced rhinitis. N Engl J Med 313:65–70PubMedCrossRefGoogle Scholar
  54. 54.
    Neeley SP, Hamann KJ, White SR, Baranowski SL, Burch RA, Leff AR (1993) Selective regulation of expression of surface adhesion molecules Mac-1, L-selectin, and VLA-4 on human eosinophils and neutrophils. Am Rev Respir Cell Mol Biol 8:633–639Google Scholar
  55. 55.
    Okuda M, Ohtsuka H (1977) Basophilic cells in allergic nasal secretions. Arch Otorhinolaryngol 214:283–289PubMedCrossRefGoogle Scholar
  56. 56.
    Oppenheim JJ, Zachariae COC, Mukaida N, Matsushima K (1991) Properties of the novel proinflammatroy supergene “"intercrine”" cytokine family. Annu Rev Immunol 9:617–648PubMedGoogle Scholar
  57. 57.
    Phillips ML, Nudelman E, Gaeta FCA, Perez M, Singhal AK, Hakomori S-I, Paulson JC (1990) ELAM-1 mediates cell adhesion by recognition of a carbohydrate ligand, sialyl-Lex. Science 250:1130–1132PubMedGoogle Scholar
  58. 58.
    Pipkorn U, Karlsson G, Enerback L (1988) The cellular response of the human allergic mucosa to natural allergen exposure. J Allergy Clin Immunol 82:1046–1054PubMedCrossRefGoogle Scholar
  59. 59.
    Rot A, Krieger M, Brunner T, Bischoff SC, Schall TJ, Dahinden CA (1992) RANTES and macrophage inflammatory protein la induce the migration and activation of normal human eosinophil granulocytes. J Exp Med 176: 1489–1495PubMedCrossRefGoogle Scholar
  60. 60.
    Schall TJ (1991) Biology of the RANTES/SIS cytokine family. Cytokine 3: 165–183PubMedCrossRefGoogle Scholar
  61. 61.
    Schall TJ, Bacon K, Toy KJ, Goeddel DV (1990) Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES. Nature 347:669–671PubMedCrossRefGoogle Scholar
  62. 62.
    Schleimer RP, Bochner BS (1991) Letter to the editor. J Immunol 147:380–381PubMedGoogle Scholar
  63. 63.
    Schleimer RP, Rutledge BK (1986) Cultured human vascular endothelial cells acquire adhesiveness for leukocytes following stimulation with interleukin-1, endotoxin, and tumor-promoting phorbol esters. J Immunol 136:649–654PubMedGoogle Scholar
  64. 64.
    Schleimer RP, Sterbinsky SA, Kaiser J, Bickel CA, Klunk DA, Tomioka K, Newman W, Luscinskas FW, Gimbrone MA Jr, McIntyre BW, Bochner BS (1992) Interleukin-4 induces adherence of human eosinophils and basophils but not neutrophils to endothelium: association with expression of VCAM-1. J Immunol 148:1086–1092PubMedGoogle Scholar
  65. 65.
    Sedgwick JB, Calhoun WJ, Vrtis RF, Bates ME, McAllister PK, Busse WW (1992) Comparison of airway and blood eosinophil function after in vivo antigen challenge. J Immunol 149:3710–3718PubMedGoogle Scholar
  66. 66.
    Spertini O, Luscinskas FW, Kansas GS, Munro JM, Griffin JD, Gimbrone MA, Tedder TF (1991) Leukocyte adhesion molecule-1 (LAM-1, L-selectin) interacts with an inducible endothelial cell ligand to support leukocyte adhesion. J Immunol 147:2565–2573PubMedGoogle Scholar
  67. 67.
    Springer TA (1990) Adhesion receptors of the immune system. Nature 346 425–434PubMedCrossRefGoogle Scholar
  68. 68.
    Tepper RI, Levinson DA, Stanger BZ, Campos-Torres J, Abbas AK, Leder P (1990) IL-4 induces allergic-like inflammatory disease and alters T cell development in transgenic mice. Cell 62:457–467PubMedCrossRefGoogle Scholar
  69. 69.
    Tepper RI, Pattengale PK, Leder P (1989) Murine interleukin4 displays potent anti-tumor acitvity in vivo. Cell 57:503–512PubMedCrossRefGoogle Scholar
  70. 70.
    Thornhill MH, Kyan-Aung U, Haskard DO (1990) IL-4 increases human endothelial cell adhesiveness for T cells but not for neutrophils. J Immunol 144:3060–3065PubMedGoogle Scholar
  71. 71.
    Vadas MA, Gamble JR, Smith WB (1992) Regulation of myeloid blood cell-endothelial interaction by cytokines. In: Harlan JM, Liu DY (eds) Adhesion: its role in inflammatory disease. Freeman, New York, pp 65–81Google Scholar
  72. 72.
    Varney V, Jacobson M, Sudderick R, Robinson D, Irani A, Schwartz L, Mackay I, Kay A, Durham S (1992) Immunohistology of the nasal mucosa following allergen-induced rhinitis. Am Rev Respir Dis 146:170–176PubMedGoogle Scholar
  73. 73.
    Walker C, Ribs S, Braun RK, Betz S, Bruijnzeel PLB (1993) Increased expression of CDllb and functional changes in eosinophils after migration across endothelial cell monolayers. J Immunol 150: 4061–4071PubMedGoogle Scholar
  74. 74.
    Walsh GM, Mermod J, Hartnell A, Kay AB, Wardlaw AJ (1991) Human eosinophil, but not neutrophil, adherence to IL-1 stimulated human umbilical vascular endothelial cells is α4ß1 (very late antigen-4) dependent. J Immunol 146: 3419–3423PubMedGoogle Scholar
  75. 75.
    Walz G, Aruffo A, Kolanus W, Bevilacqua M, Seed B (1990) Recognition by ELAM-1 of the sialyl-Lex determinant on myeloid and tumor cells. Science 250 1132–1135PubMedGoogle Scholar
  76. 76.
    Wegner CD, Gundel RH, Letts LG (1992) Expression and probable roles of cell adhesion molecules in lung inflammation. Chest 101: 34S-39SPubMedGoogle Scholar
  77. 77.
    Wegner CD, Gundel RH, Reilly P, Haynes N, Letts LG, Rothlein R (1990) Intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of asthma. Science 247:456–459PubMedGoogle Scholar
  78. 78.
    Wegner CD, Rothlein R, Clarke CC, Haynes N, Torcellini CA, La Plante AM, Averill DR, Letts LG, Gundel RH (1991) Inhaled ICAM-1 reduces antigen-induced airway hyperresponsiveness in monkeys (abstract). Am Rev Respir Dis 143: A418Google Scholar
  79. 79.
    Wein M, Bochner BS (1993) Adhesion molecule antagonists: future therapies for allergic diseases? Ent Respir J 6: 1239–1242Google Scholar
  80. 80.
    Weller PF, Rand RH, Goelz SE, Chi-Rosso G, Lobb RR (1991) Human eosinophil adherence to vascular endothelium mediated by binding to vascular cell adhesion molecule 1 and endothelial leukocyte adhesion molecule 1. Proc Natl Acad Sci USA 88: 7430–7433PubMedCrossRefGoogle Scholar
  81. 81.
    Yamada T, Ebisawa M, MacGlashan DW Jr, Bickel C, Oppenheim JJ, Bochner BS, Schleimer RP (1993) RANTES is a chemoattractant for human eosinophils (abstract). J Allergy Clin Immunol 91:692Google Scholar
  82. 82.
    Ying S, Durham SR, Barkans J, Masuyama K, Jacobson M, Rak S, Löwhagen O, Moqbel R, Kay AB, Hamid QA (1993) T cells are the principal source of interleukin-5 mRNA in allergen-induced rhinitis. Am J Respir Cell Mol Biol 9:356–360PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • F. M. Baroody
    • 1
    • 3
  • B. -J. Lee
    • 1
    • 3
  • M. C. Lim
    • 1
    • 3
  • B. S. Bochner
    • 2
    • 3
  1. 1.Department of Otolaryngology - Head and Neck SurgeryThe Johns Hopkins School of MedicineBalitmoreUSA
  2. 2.Department of Medicine, Division of Clinical ImmunologyThe Johns Hopkins University School of MedicineBaltimoreUSA
  3. 3.Johns Hopkins Asthma and Allergy CenterClinical Immunology Unit Office 3BaltimoreUSA

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