Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens
Taruna Madan, … , Kenneth B.M. Reid, P. Usha Sarma
Taruna Madan, … , Kenneth B.M. Reid, P. Usha Sarma
Published February 15, 2001
Citation Information: J Clin Invest. 2001;107(4):467-475. https://doi.org/10.1172/JCI10124.
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Article

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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Figure 6

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Ratio of lung EPO activity (estimated in the lung cell suspensions by a ...
Ratio of lung EPO activity (estimated in the lung cell suspensions by a colorimetric substrate assay as described in Methods) of the 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) to their respective controls as observed on day 0, 4, 10, and 16 of the treatment study. Each value represents a mean of nine readings (triplicate values from three animals of each group). Absorbance values ± SD for the control groups observed on day 16 are as follows: untreated control, 0.252 ± 0.012; SP-A–treated control, 0.236 ± 0.015; SP-D–treated control, 0.242 ± 0.012; rSP-D–treated control, 0.225 ± 0.007; and BSA-treated control, 0.226 ± 0.001. AP < 0.05 compared with the values of the untreated ABPA mice on the same day.