Pulmonary surfactant, which covers the peripheral airway. is a mixture of lipids and proteins. The hydrophilic surfactant proteins A (SPA) and D (SP-D) play important roles in host defense mechanisms of the lung. These proteins belong to a collectin Subgroup in which lectin domains are associated with collagenous structures. Collectins involve mannose-binding lectin, and are considered to function in innate immune systems. SP-A and SP-D interact with various microorganisms and pathogen-derived components. They act as opsonins by binding and agglutinating pathogens. The lung collectins also possess direct inhibitory effects on bacterial growth. SP-A and SP-D associate with immune cells, and activate various cellular functions. The direct interactions of SP-A and SP-D with macrophages result in modulation of phagocytosis or the production of reactive oxygen species. Moreover. by associating with cell surface pattern-recognition receptors. SP-A and SP-D regulate inflammatory cellular responses such as the release of lipopolysaccharides-induced proinflammatory cytokines. Animal models of SP-A or SP-D-deficiency reveal significant defect in host defense. Significant susceptibility to bacterial and viral infections. delayed microbial clearance. and overexpression of proinflammatory cytokines are observed in SP-A or SP-D knockout mice. A more complete understanding of the mechanisms is required, but the biological relevance of SP-A and SP-D against various respiratory infections has been increasingly recognized. (C) 2004 Elsevier Ltd. All rights reserved.