Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens
Taruna Madan, Uday Kishore, Mamta Singh, Peter Strong, Howard Clark, Ejaj M. Hussain, Kenneth B.M. Reid, P. Usha Sarma
Taruna Madan, Uday Kishore, Mamta Singh, Peter Strong, Howard Clark, Ejaj M. Hussain, Kenneth B.M. Reid, P. Usha Sarma
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Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens

Abstract

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic disorder caused by an opportunistic fungal pathogen, Aspergillus fumigatus (Afu). Lung surfactant proteins SP-A and SP-D can interact with the glycosylated antigens and allergens of Afu, inhibit specific IgE binding to these allergens, and block histamine release from sensitized basophils. We have now examined the therapeutic effect of exogenous administration of human SP-A, SP-D, and a recombinant fragment of SP-D (rSP-D), in a murine model of pulmonary hypersensitivity induced by Afu antigens and allergens, which resembles human ABPA immunologically. The ABPA mice exhibited high levels of Afu-specific IgG and IgE, blood eosinophilia, extensive infiltration of lymphocytes and eosinophils in the lung sections, and a Th2 cytokine response. Treatment with SP-A, SP-D, and rSP-D lowered blood eosinophilia, pulmonary infiltration, and specific Ab levels considerably, which persisted up to 4 days in the SP-A–treated ABPA mice, and up to 16 days in the SP-D– or rSP-D–treated ABPA mice. The levels of IL-2, IL-4, and IL-5 were decreased, while the level of IFN-γ was raised in the splenic supernatants of the treated mice, indicating a marked shift from Th2 to Th1 response. These results clearly implicate pulmonary SP-A and SP-D in the modulation of allergic reactions.

Authors

Taruna Madan, Uday Kishore, Mamta Singh, Peter Strong, Howard Clark, Ejaj M. Hussain, Kenneth B.M. Reid, P. Usha Sarma

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Ratios of IL-2, IL-4, IL-5, and IFN-γ in splenic supernatants from untre...
Ratios of IL-2, IL-4, IL-5, and IFN-γ in splenic supernatants from untreated ABPA mice (black bars), SP-A–treated ABPA mice (white bars), SP-D–treated ABPA mice (dark gray bars), rSP-D–treated ABPA mice (light gray bars), and BSA-treated ABPA mice (medium gray bars) groups to their respective control groups as observed on day 10 of the treatment study. Each value represents a mean of nine readings (triplicate values from three animals of each group). Cytokine levels ± SD for the control groups observed on day 10 are as follows: untreated control, IL-2: 19.286 ± 0.827 pg/ml; IL-4: 42.036 ± 2.101 pg/ml; IL-5: 22.436 ± 1.121 pg/ml; IFN-γ: 33.281 ± 1.691 ng/ml; SP-A–treated control, IL-2: 14.529 ± 0.726 pg/ml; IL-4: 39.048 ± 1.952 pg/ml; IL-5: 18.229 ± 0.911 pg/ml; IFN-γ: 29.476 ± 1.473 ng/ml; SP-D–treated control, IL-2: 15.016 ± 0.750 pg/ml; IL-4: 36.725 ± 1.837 pg/ml; IL-5: 17.548 ± 0.877 pg/ml; IFN-γ: 28.359 ± 1.417 ng/ml; rSP-D–treated control, IL-2: 14.856 ± 0.742 pg/ml; IL-4: 37.543 ± 1.877 pg/ml; IL-5: 19.212 ± 0.960 pg/ml; IFN-γ: 29.021 ± 1.451 ng/ml; and BSA-treated control, IL-2: 19.893 ± 0.815 pg/ml; IL-4: 49.135 ± 1.962 pg/ml; IL-5: 28.431 ± 0.989 pg/ml; IFN-γ: 28.941 ± 1.216 ng/ml. AP < 0.05 compared with the values of the untreated ABPA mice on the same day.