Intranasal delivery of a truncated recombinant human SP‐D is effective at down‐regulating allergic hypersensitivity in mice sensitized to allergens of Aspergillus fumigatus

C57BL/6 mice were sensitized to Aspergillus fumigatus 1‐week culture filtrate, which is rich in the non‐glycosylated allergen Asp f1, a major allergen in allergic bronchopulmonary aspergillosis (ABPA). A comparison of the effect of treatment of allergen challenged mice by intranasal administration of a 60‐kDa truncated recombinant form of human SP‐D (rfhSP‐D) or recombinant full length SP‐A (rhSP‐A) was undertaken. Treatment with rfhSP‐D produced significant reduction in IgE, IgG1 and peripheral blood eosinophilia and treatment with rfhSP‐D, but not rhSP‐A resulted in a significant reduction in airway hyperresponsiveness as measured by whole body plethysmography. Lung histology revealed less peribronchial lymphocytic infiltration in mice treated with rfhSP‐D. Intracellular cytokine staining of spleen homogenates showed increases in IL‐12 and IFN‐γ and decrease in IL‐4. The level of endogenous mouse SP‐D was elevated sixfold in the lungs of sensitized mice and was not affected by treatment with rfhSP‐D. Taken with our previous studies, with a BALB/c mouse model of ABPA using a 3‐week A. fumigatus culture filtrate, the present results show that rfhSP‐D can suppress the development of allergic symptoms in sensitized mice independent of genetic background and using a different preparation of A. fumigatus allergens.

[1]  D. Corry,et al.  The Th2 lymphocyte products IL-4 and IL-13 rapidly induce airway hyperresponsiveness through direct effects on resident airway cells. , 2002, American journal of respiratory cell and molecular biology.

[2]  U. Kishore,et al.  Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens. , 2001, The Journal of clinical investigation.

[3]  S. Russo,et al.  Aspergillus fumigatus-induced allergic airway inflammation alters surfactant homeostasis and lung function in BALB/c mice. , 2001, American journal of respiratory cell and molecular biology.

[4]  Stephen T Holgate,et al.  Effects of recombinant human interleukin-12 on eosinophils, airway hyper-responsiveness, and the late asthmatic response , 2000, The Lancet.

[5]  Y. Fukushima,et al.  Increased levels of surfactant protein A and D in bronchoalveolar lavage fluids in patients with bronchial asthma. , 2000, The European respiratory journal.

[6]  L. Hazlett,et al.  Increased severity of Pseudomonas aeruginosa corneal infection in strains of mice designated as Th1 versus Th2 responsive. , 2000, Investigative ophthalmology & visual science.

[7]  D. Klinman,et al.  Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides. , 1999, Journal of immunology.

[8]  P. Eggleton,et al.  Lung surfactant proteins involved in innate immunity. , 1999, Current opinion in immunology.

[9]  E. Crouch Structure, biologic properties, and expression of surfactant protein D (SP-D). , 1998, Biochimica et biophysica acta.

[10]  K. Reid Interactions of surfactant protein D with pathogens, allergens and phagocytes. , 1998, Biochimica et biophysica acta.

[11]  E. Crouch Collectins and pulmonary host defense. , 1998, American journal of respiratory cell and molecular biology.

[12]  B. Varkey Beware of the fungus. , 1998, WMJ : official publication of the State Medical Society of Wisconsin.

[13]  R. Crameri,et al.  Differential IgE recognition of recombinant Aspergillus fumigatus allergens by cystic fibrosis patients with allergic bronchopulmonary aspergillosis or Aspergillus allergy , 1998, European journal of immunology.

[14]  H. Lei,et al.  Inhibitory effect of pulmonary surfactant proteins A and D on allergen-induced lymphocyte proliferation and histamine release in children with asthma. , 1998, American journal of respiratory and critical care medicine.

[15]  U. Kishore,et al.  Lung surfactant proteins A and D can inhibit specific IgE binding to the allergens of Aspergillus fumigatus and block allergen‐induced histamine release from human basophils , 1997, Clinical and experimental immunology.

[16]  E. Gelfand,et al.  Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. , 1997, American journal of respiratory and critical care medicine.

[17]  U. Kishore,et al.  Interaction of human lung surfactant proteins A and D with mite (Dermatophagoides pteronyssinus) allergens , 1996, Clinical and experimental immunology.

[18]  F. Brombacher,et al.  Immune Responses of IL‐4, IL‐5, IL‐6 Deficient Mice , 1995, Immunological reviews.

[19]  F. Finkelman,et al.  Interleukin 12 inhibits antigen-induced airway hyperresponsiveness, inflammation, and Th2 cytokine expression in mice , 1995, The Journal of experimental medicine.

[20]  T. S. van der Werf,et al.  Review of fungus-induced asthmatic reactions. , 1995, American journal of respiratory and critical care medicine.

[21]  L. Lichtenstein,et al.  Immunological aspects of allergic asthma. , 1994, Annual review of immunology.

[22]  E. Unanue,et al.  Interleukin 12 and tumor necrosis factor alpha are costimulators of interferon gamma production by natural killer cells in severe combined immunodeficiency mice with listeriosis, and interleukin 10 is a physiologic antagonist. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[23]  M. Chapman,et al.  Selective expression of a major allergen and cytotoxin, Asp f I, in Aspergillus fumigatus. Implications for the immunopathogenesis of Aspergillus-related diseases. , 1992, Journal of immunology.

[24]  S. Durham,et al.  Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. , 1992, The New England journal of medicine.

[25]  K. Blaser,et al.  Activated T cells and eosinophilia in bronchoalveolar lavages from subjects with asthma correlated with disease severity. , 1991, The Journal of allergy and clinical immunology.

[26]  R. Slavin,et al.  Variability in parameters of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis. , 1991, The Journal of allergy and clinical immunology.

[27]  M. Elstad Aspergillosis and lung defenses. , 1991, Seminars in respiratory infections.

[28]  K. Arai,et al.  IgE production by normal human lymphocytes is induced by interleukin 4 and suppressed by interferons gamma and alpha and prostaglandin E2. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[29]  J. Engel,et al.  Macromolecular organization of natural and recombinant lung surfactant protein SP 28-36. Structural homology with the complement factor C1q. , 1988, Journal of molecular biology.