The lung collectins, SP-A and SP-D, are important components of the innate immune response to microbial challenge and participate in other aspects of immune and inflammatory regulation within the lung. Both proteins bind to surface structures expressed by a wide variety of microorganisms and have the capacity to modulate multiple leukocyte functions, including the enhanced internalization and killing of certain microorganisms in vitro. In addition, transgenic mice with deficiencies in SP-A and SP-D show defective or altered responses to challenge with bacterial, fungal, and viral microorganisms and to bacterial lipopolysaccharides in vivo. Thus collectins could play particularly important roles in settings of inadequate or impaired specific immunity, and acquired alterations in the levels of active collectins within the airspaces and distal airways may increase susceptibility to infection.

We tested the hypothesis that pulmonary surfactant-associated lectins -surfactant proteins A and D (SP-A, and -D) contribute to initial protective mechanisms against influenza A viruses (IAVs). SP-D potently inhibited hemagglutination activity of several strains of IAV as well as causing viral aggregation. SP-D enhanced neutrophil binding of 1AV and neutrophil respiratory burst responses to the virus. Neutrophil dysfunction resulting from 1AV exposure was diminished when the virus was pre-incubated with SP-D. Each of these effects was mediated by the calcium-dependent carbohydrate-binding property of SP-D. Native SP-D preparations of both human and rat origin, as well as recombinant rat SP-D, had similar activity. SP-A also inhibited IAV hemagglutination activity. We have previously reported that related mammalian serum lectins (mannose-binding lectin [MBL] and conglutinin) have similar effects. SP-D was at least 10-fold more potent at causing hemagglutination inhibition than were SP-A or MBL. SP-D was shown to contribute to potent anti-IAV activity of human bronchoalveolar lavage fluid. These results suggest that SP-D-alone, and in conjunction with SP-A and phagocytic cells-constitutes an important component of the natural immune response to 1AV infection within the respiratory tract. (J. Clin. Invest.