Search tips
Search criteria 


Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. 1997 March 1; 99(5): 915–925.
PMCID: PMC507899

Absence of Fc epsilonRI alpha chain results in upregulation of Fc gammaRIII-dependent mast cell degranulation and anaphylaxis. Evidence of competition between Fc epsilonRI and Fc gammaRIII for limiting amounts of FcR beta and gamma chains.


In mouse mast cells, both Fc epsilonRI and Fc gammaRIII are alpha beta gamma2 tetrameric complexes in which different alpha chains confer IgE or IgG ligand recognition while the signaling FcR beta and gamma chains are identical. We used primarily noninvasive techniques (changes in body temperature, dye extravasation) to assess systemic anaphylactic responses in nonanesthetized wild-type, Fc epsilonRI alpha chain -/- and FcR gamma chain -/- mice. We confirm that systemic anaphylaxis in mice can be mediated largely through IgG1 and Fc gammaRIII and we provide direct evidence that these responses reflect activation of Fc gammaRIII rather than Fc gammaRI. Furthermore, we show that Fc gammaRIII-dependent responses are more intense in normal than in congenic mast cell-deficient KitW/KitW-v mice, indicating that Fc gammaRIII responses have mast cell-dependent and -independent components. Finally, we demonstrate that the upregulation of cell surface expression of Fc gammaRIII seen in Fc epsilonRI alpha chain -/- mice corresponds to an increased association of Fc gammaRIII alpha chains with FcR beta and gamma chains and is associated with enhanced Fc gammaRIII-dependent mast cell degranulation and systemic anaphylactic responses. Therefore, the phenotype of the Fc epsilonRI alpha chain -/- mice suggests that expression of Fc epsilonRI and Fc gammaRIII is limited by availability of the FcR beta and gamma chains and that, in normal mice, changes in the expression of one receptor (Fc epsilonRI) may influence the expression of functional responses dependent on the other (Fc gammaRIII).

Full Text

The Full Text of this article is available as a PDF (290K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Miyajima I, Dombrowicz D, Martin TR, Ravetch JV, Kinet JP, Galli SJ. Systemic anaphylaxis in the mouse can be mediated largely through IgG1 and Fc gammaRIII. Assessment of the cardiopulmonary changes, mast cell degranulation, and death associated with active or IgE- or IgG1-dependent passive anaphylaxis. J Clin Invest. 1997 Mar 1;99(5):901–914. [PMC free article] [PubMed]
  • Dombrowicz D, Flamand V, Brigman KK, Koller BH, Kinet JP. Abolition of anaphylaxis by targeted disruption of the high affinity immunoglobulin E receptor alpha chain gene. Cell. 1993 Dec 3;75(5):969–976. [PubMed]
  • Takai T, Li M, Sylvestre D, Clynes R, Ravetch JV. FcR gamma chain deletion results in pleiotrophic effector cell defects. Cell. 1994 Feb 11;76(3):519–529. [PubMed]
  • Ravetch JV. Fc receptors: rubor redux. Cell. 1994 Aug 26;78(4):553–560. [PubMed]
  • Jacoby W, Cammarata PV, Findlay S, Pincus SH. Anaphylaxis in mast cell-deficient mice. J Invest Dermatol. 1984 Oct;83(4):302–304. [PubMed]
  • Ha TY, Reed ND, Crowle PK. Immune response potential of mast cell-deficient W/Wv mice. Int Arch Allergy Appl Immunol. 1986;80(1):85–94. [PubMed]
  • Ha TY, Reed ND. Systemic anaphylaxis in mast-cell-deficient mice of W/Wv and Sl/Sld genotypes. Exp Cell Biol. 1987;55(2):63–68. [PubMed]
  • Takeishi T, Martin TR, Katona IM, Finkelman FD, Galli SJ. Differences in the expression of the cardiopulmonary alterations associated with anti-immunoglobulin E-induced or active anaphylaxis in mast cell-deficient and normal mice. Mast cells are not required for the cardiopulmonary changes associated with certain fatal anaphylactic responses. J Clin Invest. 1991 Aug;88(2):598–608. [PMC free article] [PubMed]
  • Martin TR, Ando A, Takeishi T, Katona IM, Drazen JM, Galli SJ. Mast cells contribute to the changes in heart rate, but not hypotension or death, associated with active anaphylaxis in mice. J Immunol. 1993 Jul 1;151(1):367–376. [PubMed]
  • Kitamura Y, Go S, Hatanaka K. Decrease of mast cells in W/Wv mice and their increase by bone marrow transplantation. Blood. 1978 Aug;52(2):447–452. [PubMed]
  • Galli SJ, Zsebo KM, Geissler EN. The kit ligand, stem cell factor. Adv Immunol. 1994;55:1–96. [PubMed]
  • Unkeless JC. Characterization of a monoclonal antibody directed against mouse macrophage and lymphocyte Fc receptors. J Exp Med. 1979 Sep 19;150(3):580–596. [PMC free article] [PubMed]
  • George AJ, Titus JA, Jost CR, Kurucz I, Perez P, Andrew SM, Nicholls PJ, Huston JS, Segal DM. Redirection of T cell-mediated cytotoxicity by a recombinant single-chain Fv molecule. J Immunol. 1994 Feb 15;152(4):1802–1811. [PubMed]
  • Flores-Romo L, Shields J, Humbert Y, Graber P, Aubry JP, Gauchat JF, Ayala G, Allet B, Chavez M, Bazin H, et al. Inhibition of an in vivo antigen-specific IgE response by antibodies to CD23. Science. 1993 Aug 20;261(5124):1038–1041. [PubMed]
  • Schwartz LB, Yunginger JW, Miller J, Bokhari R, Dull D. Time course of appearance and disappearance of human mast cell tryptase in the circulation after anaphylaxis. J Clin Invest. 1989 May;83(5):1551–1555. [PMC free article] [PubMed]
  • FRIMMER M, MUELLER FW. [Usefulness and limitations of dye methods in the determination of increased permeability of the skin capillaires]. Med Exp Int J Exp Med. 1962;6:327–330. [PubMed]
  • Wershil BK, Mekori YA, Murakami T, Galli SJ. 125I-fibrin deposition in IgE-dependent immediate hypersensitivity reactions in mouse skin. Demonstration of the role of mast cells using genetically mast cell-deficient mice locally reconstituted with cultured mast cells. J Immunol. 1987 Oct 15;139(8):2605–2614. [PubMed]
  • Martin TR, Gerard NP, Galli SJ, Drazen JM. Pulmonary responses to bronchoconstrictor agonists in the mouse. J Appl Physiol (1985) 1988 Jun;64(6):2318–2323. [PubMed]
  • Martin TR, Galli SJ, Katona IM, Drazen JM. Role of mast cells in anaphylaxis. Evidence for the importance of mast cells in the cardiopulmonary alterations and death induced by anti-IgE in mice. J Clin Invest. 1989 Apr;83(4):1375–1383. [PMC free article] [PubMed]
  • Galli SJ, Arizono N, Murakami T, Dvorak AM, Fox JG. Development of large numbers of mast cells at sites of idiopathic chronic dermatitis in genetically mast cell-deficient WBB6F1-W/Wv mice. Blood. 1987 Jun;69(6):1661–1666. [PubMed]
  • Wershil BK, Murakami T, Galli SJ. Mast cell-dependent amplification of an immunologically nonspecific inflammatory response. Mast cells are required for the full expression of cutaneous acute inflammation induced by phorbol 12-myristate 13-acetate. J Immunol. 1988 Apr 1;140(7):2356–2360. [PubMed]
  • Rivera J, Kinet JP, Kim J, Pucillo C, Metzger H. Studies with a monoclonal antibody to the beta subunit of the receptor with high affinity for immunoglobulin E. Mol Immunol. 1988 Jul;25(7):647–661. [PubMed]
  • Orloff DG, Ra CS, Frank SJ, Klausner RD, Kinet JP. Family of disulphide-linked dimers containing the zeta and eta chains of the T-cell receptor and the gamma chain of Fc receptors. Nature. 1990 Sep 13;347(6289):189–191. [PubMed]
  • Takizawa F, Adamczewski M, Kinet JP. Identification of the low affinity receptor for immunoglobulin E on mouse mast cells and macrophages as Fc gamma RII and Fc gamma RIII. J Exp Med. 1992 Aug 1;176(2):469–475. [PMC free article] [PubMed]
  • Kurosaki T, Gander I, Wirthmueller U, Ravetch JV. The beta subunit of the Fc epsilon RI is associated with the Fc gamma RIII on mast cells. J Exp Med. 1992 Feb 1;175(2):447–451. [PMC free article] [PubMed]
  • Lin S, Cicala C, Scharenberg AM, Kinet JP. The Fc(epsilon)RIbeta subunit functions as an amplifier of Fc(epsilon)RIgamma-mediated cell activation signals. Cell. 1996 Jun 28;85(7):985–995. [PubMed]

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