Surfactant protein D: A therapeutic target for allergic airway diseases

Surfactant protein D (SP-D), expressed in respiratory epithelium, is important for modulating both innate and adaptive immunity against inhaled allergens. This chapter evaluates the key immunomodulatory role of SP-D in allergic airway inflammatory events. Studies have shown that SP-D ameliorated various cellular mechanisms implicated in pulmonary allergic reactions, including allergic eosinophilia through induction of apoptosis and clearance of activated eosinophils, and inhibition of basophils activation. In addition, blocking allergen-specific IgE synthesis, T cell proliferation, and hindrance to the binding of allergen-IgE complex to B lymphocytes are also brought about by SP-D. In vitro, a recombinant fragment of human SP-D, composed of homotrimeric neck and C-type lectin domains (rfhSP-D), binds to allergens derived from Aspergillus fumigatus, house dust mite and grass pollen in a calcium-dependent manner and inhibits specific IgE interaction with allergens. Murine models of hypersensitivity reactions, when treated with rfhSP-D, showed reduced levels of IgE, clearance of peripheral and pulmonary eosinophilia, and Th2 polarisation to Th1 type. SP-D knock-out mice accordingly show hypereosinophilia and predominantly exaggerated Th2 response following allergen challenge; these features can be ameliorated by rfhSP-D treatment. The current state of the filed appears to suggest that rfhSP-D is an excellent therapeutic immunomodulator in airway allergic diseases.