Search tips
Search criteria 


Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. 1996 March 15; 97(6): 1398–1408.
PMCID: PMC507198

Passive transfer of immediate hypersensitivity and airway hyperresponsiveness by allergen-specific immunoglobulin (Ig) E and IgG1 in mice.


In a proportion of atopic asthmatics, exposure to a relevant antigen is followed by chronic inflammation in the airways leading to altered airway responsiveness (AR). However, the mechanisms underlying the development of airway hyperresponsiveness still remain unclear. To elucidate the relationship between IgE-mediated reactions and airway hyperresponsiveness, a murine model of passive sensitization and airway challenge with ovalbumin (OVA) was developed using anti-OVA IgE and IgG antibodies from murine B cell hybridomas. Passive sensitization by intravenous injection of anti-OVA IgE resulted in immediate cutaneous hypersensitivity and, after airway challenge with OVA on two consecutive days, increased AR in BALB/c and SJL mice. Increased numbers of eosinophils were observed in bronchoalveolar lavage fluid, in cells extracted from the lungs, and in the peribronchial areas of BALB/c mice passively sensitized with IgE and challenged through the airways compared with nonsensitized mice. Eosinophil peroxidase activity was also elevated in lung tissue from these mice. Passive sensitization with anti-OVA IgG1 but not IgG2a or IgG3 was similarly associated with development of skin test reactivity and increased AR after airway challenge, accompanied by an increase in eosinophils in bronchoalveolar lavage fluid. These data suggest that IgE/IgG1-mediated reactions together with local challenge with antigen can result in allergic inflammation resulting in altered airway function.

Full Text

The Full Text of this article is available as a PDF (267K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Zweiman B. The late-phase reaction: role of IgE, its receptor and cytokines. Curr Opin Immunol. 1993 Dec;5(6):950–955. [PubMed]
  • Müller KM, Jaunin F, Masouyé I, Saurat JH, Hauser C. Th2 cells mediate IL-4-dependent local tissue inflammation. J Immunol. 1993 Jun 15;150(12):5576–5584. [PubMed]
  • Bradley BL, Azzawi M, Jacobson M, Assoufi B, Collins JV, Irani AM, Schwartz LB, Durham SR, Jeffery PK, Kay AB. Eosinophils, T-lymphocytes, mast cells, neutrophils, and macrophages in bronchial biopsy specimens from atopic subjects with asthma: comparison with biopsy specimens from atopic subjects without asthma and normal control subjects and relationship to bronchial hyperresponsiveness. J Allergy Clin Immunol. 1991 Oct;88(4):661–674. [PubMed]
  • Bentley AM, Menz G, Storz C, Robinson DS, Bradley B, Jeffery PK, Durham SR, Kay AB. Identification of T lymphocytes, macrophages, and activated eosinophils in the bronchial mucosa in intrinsic asthma. Relationship to symptoms and bronchial responsiveness. Am Rev Respir Dis. 1992 Aug;146(2):500–506. [PubMed]
  • Robinson DS, Hamid Q, Ying S, Tsicopoulos A, Barkans J, Bentley AM, Corrigan C, Durham SR, Kay AB. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med. 1992 Jan 30;326(5):298–304. [PubMed]
  • Corrigan CJ, Kay AB. T cells and eosinophils in the pathogenesis of asthma. Immunol Today. 1992 Dec;13(12):501–507. [PubMed]
  • Renz H, Smith HR, Henson JE, Ray BS, Irvin CG, Gelfand EW. Aerosolized antigen exposure without adjuvant causes increased IgE production and increased airway responsiveness in the mouse. J Allergy Clin Immunol. 1992 Jun;89(6):1127–1138. [PubMed]
  • Renz H, Saloga J, Bradley KL, Loader JE, Greenstein JL, Larsen G, Gelfand EW. Specific V beta T cell subsets mediate the immediate hypersensitivity response to ragweed allergen. J Immunol. 1993 Aug 15;151(4):1907–1917. [PubMed]
  • Saloga J, Renz H, Lack G, Bradley KL, Greenstein JL, Larsen G, Gelfand EW. Development and transfer of immediate cutaneous hypersensitivity in mice exposed to aerosolized antigen. J Clin Invest. 1993 Jan;91(1):133–140. [PMC free article] [PubMed]
  • Waserman S, Olivenstein R, Renzi P, Xu LJ, Martin JG. The relationship between late asthmatic responses and antigen-specific immunoglobulin. J Allergy Clin Immunol. 1992 Oct;90(4 Pt 1):661–669. [PubMed]
  • Behrens BL, Clark RA, Marsh W, Larsen GL. Modulation of the late asthmatic response by antigen-specific immunoglobulin G in an animal model. Am Rev Respir Dis. 1984 Dec;130(6):1134–1139. [PubMed]
  • Oettgen HC, Martin TR, Wynshaw-Boris A, Deng C, Drazen JM, Leder P. Active anaphylaxis in IgE-deficient mice. Nature. 1994 Aug 4;370(6488):367–370. [PubMed]
  • Ovary Z, Vaz NM, Warner NL. Passive anaphylaxis in mice with gamma-G antibodies. V. Competitive effects of different immunoglobulins and inhibition of reactions with antiglobulin sera. Immunology. 1970 Nov;19(5):715–727. [PubMed]
  • Daëron M, Prouvost-Danon A, Voisin GA. Mast cell membrane antigens and Fc receptors in anaphylaxis. II. Functionally distinct receptors for IgG and for IgE on mouse mast cells. Cell Immunol. 1980 Jan;49(1):178–189. [PubMed]
  • Rittenberg MB, Amkraut AA. Immunogenicity of trinitrophenyl-hemocyanin: production of primary and secondary anti-hapten precipitins. J Immunol. 1966 Sep;97(3):421–430. [PubMed]
  • Gefter ML, Margulies DH, Scharff MD. A simple method for polyethylene glycol-promoted hybridization of mouse myeloma cells. Somatic Cell Genet. 1977 Mar;3(2):231–236. [PubMed]
  • Larsen GL, Renz H, Loader JE, Bradley KL, Gelfand EW. Airway response to electrical field stimulation in sensitized inbred mice. Passive transfer of increased responsiveness with peribronchial lymph nodes. J Clin Invest. 1992 Mar;89(3):747–752. [PMC free article] [PubMed]
  • Lavnikova N, Drapier JC, Laskin DL. A single exogenous stimulus activates resident rat macrophages for nitric oxide production and tumor cytotoxicity. J Leukoc Biol. 1993 Oct;54(4):322–328. [PubMed]
  • Strath M, Warren DJ, Sanderson CJ. Detection of eosinophils using an eosinophil peroxidase assay. Its use as an assay for eosinophil differentiation factors. J Immunol Methods. 1985 Nov 7;83(2):209–215. [PubMed]
  • Rothstein TL, Gefter ML. Affinity analysis of idiotype-positive and idiotype-negative Ars-binding hybridoma proteins and Ars-immune sera. Mol Immunol. 1983 Feb;20(2):161–168. [PubMed]
  • Holt PG, Rose AH, Batty JE, Turner KJ. Induction of adjuvant-independent IgE responses in inbred mice: primary, secondary, and persistent IgE responses to ovalbumin and ovomucoid. Int Arch Allergy Appl Immunol. 1981;65(1):42–50. [PubMed]
  • Saloga J, Renz H, Larsen GL, Gelfand EW. Increased airways responsiveness in mice depends on local challenge with antigen. Am J Respir Crit Care Med. 1994 Jan;149(1):65–70. [PubMed]
  • Gavett SH, Chen X, Finkelman F, Wills-Karp M. Depletion of murine CD4+ T lymphocytes prevents antigen-induced airway hyperreactivity and pulmonary eosinophilia. Am J Respir Cell Mol Biol. 1994 Jun;10(6):587–593. [PubMed]
  • Renzi PM, Olivenstein R, Martin JG. Effect of dexamethasone on airway inflammation and responsiveness after antigen challenge of the rat. Am Rev Respir Dis. 1993 Oct;148(4 Pt 1):932–939. [PubMed]
  • Laberge S, Rabb H, Issekutz TB, Martin JG. Role of VLA-4 and LFA-1 in allergen-induced airway hyperresponsiveness and lung inflammation in the rat. Am J Respir Crit Care Med. 1995 Mar;151(3 Pt 1):822–829. [PubMed]
  • Larsen GL, Fame TM, Renz H, Loader JE, Graves J, Hill M, Gelfand EW. Increased acetylcholine release in tracheas from allergen-exposed IgE-immune mice. Am J Physiol. 1994 Mar;266(3 Pt 1):L263–L270. [PubMed]
  • Pretolani M, Ruffié C, Joseph D, Campos MG, Church MK, Lefort J, Vargaftig BB. Role of eosinophil activation in the bronchial reactivity of allergic guinea pigs. Am J Respir Crit Care Med. 1994 May;149(5):1167–1174. [PubMed]
  • Malynn BA, Wortis HH. Role of antigen-specific B cells in the induction of SRBC-specific T cell proliferation. J Immunol. 1984 May;132(5):2253–2258. [PubMed]
  • Rock KL, Benacerraf B, Abbas AK. Antigen presentation by hapten-specific B lymphocytes. I. Role of surface immunoglobulin receptors. J Exp Med. 1984 Oct 1;160(4):1102–1113. [PMC free article] [PubMed]
  • Maurer D, Ebner C, Reininger B, Fiebiger E, Kraft D, Kinet JP, Stingl G. The high affinity IgE receptor (Fc epsilon RI) mediates IgE-dependent allergen presentation. J Immunol. 1995 Jun 15;154(12):6285–6290. [PubMed]
  • Kehry MR, Yamashita LC. Low-affinity IgE receptor (CD23) function on mouse B cells: role in IgE-dependent antigen focusing. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7556–7560. [PubMed]
  • Ptak W, Geba GP, Askenase PW. Initiation of delayed-type hypersensitivity by low doses of monoclonal IgE antibody. Mediation by serotonin and inhibition by histamine. J Immunol. 1991 Jun 1;146(11):3929–3936. [PubMed]
  • Dolovich J, Hargreave FE, Chalmers R, Shier KJ, Gauldie J, Bienenstock J. Late cutaneous allergic responses in isolated IgE-dependent reactions. J Allergy Clin Immunol. 1973 Jul;52(1):38–46. [PubMed]
  • Young JD, Liu CC, Butler G, Cohn ZA, Galli SJ. Identification, purification, and characterization of a mast cell-associated cytolytic factor related to tumor necrosis factor. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9175–9179. [PubMed]
  • Brown MA, Pierce JH, Watson CJ, Falco J, Ihle JN, Paul WE. B cell stimulatory factor-1/interleukin-4 mRNA is expressed by normal and transformed mast cells. Cell. 1987 Aug 28;50(5):809–818. [PubMed]
  • Humphries RK, Abraham S, Krystal G, Lansdorp P, Lemoine F, Eaves CJ. Activation of multiple hemopoietic growth factor genes in Abelson virus-transformed myeloid cells. Exp Hematol. 1988 Oct;16(9):774–781. [PubMed]
  • Conrad DH, Squire CM, Bartlett WC, Dierks SE. Fc epsilon receptors. Curr Opin Immunol. 1991 Dec;3(6):859–864. [PubMed]
  • Tomassini M, Tsicopoulos A, Tai PC, Gruart V, Tonnel AB, Prin L, Capron A, Capron M. Release of granule proteins by eosinophils from allergic and nonallergic patients with eosinophilia on immunoglobulin-dependent activation. J Allergy Clin Immunol. 1991 Sep;88(3 Pt 1):365–375. [PubMed]
  • Truong MJ, Gruart V, Kusnierz JP, Papin JP, Loiseau S, Capron A, Capron M. Human neutrophils express immunoglobulin E (IgE)-binding proteins (Mac-2/epsilon BP) of the S-type lectin family: role in IgE-dependent activation. J Exp Med. 1993 Jan 1;177(1):243–248. [PMC free article] [PubMed]
  • Sertl K, Kowalski ML, Slater J, Kaliner MA. Passive sensitization and antigen challenge increase vascular permeability in rat airways. Am Rev Respir Dis. 1988 Nov;138(5):1295–1299. [PubMed]
  • Sorkness R, Johns K, Castleman WL, Lemanske RF., Jr Late pulmonary allergic responses in actively but not passively IgE-sensitized rats. J Appl Physiol (1985) 1990 Sep;69(3):1012–1021. [PubMed]
  • Renz H, Gelfand EW. T-cell receptor V elements regulate murine IgE production and airways responsiveness. Allergy. 1992 Aug;47(4 Pt 1):270–276. [PubMed]
  • Tigelaar RE, Vaz NM, Ovary Z. Immunoglobulin receptors on mouse mast cells. J Immunol. 1971 Mar;106(3):661–672. [PubMed]
  • Dessaint JP, Capron A. IgE and inflammatory cells: the cellular networks in allergy. Int Arch Allergy Appl Immunol. 1989;90 (Suppl 1):28–31. [PubMed]
  • Capron M, Capron A, Goetzl EJ, Austen KF. Tetrapeptides of the eosinophil chemotactic factor of anaphylaxis (ECF-A) enhance eosinophil Fc receptor. Nature. 1981 Jan 1;289(5793):71–73. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation