Priority Research Area Infections
Mission Projects Funding Techniques Publications Staff
Pulmonary surfactant is a lipoprotein complex synthesized and secreted by alveolar type II cells that reduces the surface tension at the lung alveolar air-liquid interface, a function that requires both surfactant lipids and the hydrophobic proteins, surfactant protein B and SP-C. Two other surfactant proteins, SP-A and SP-D, belong to a group of collagenous carbohydrate-binding proteins known as collectins that mediate a variety of immune cell functions in vitro and in vivo.
For example, SP-A and SP-D stimulate phagocytosis and chemotaxis and regulate cytokine production by multiple immune cells. SP-A-deficient mice have an enhanced susceptibility to infection to pulmonary infection with bacterial and fungal pathogens and collectin replacement in these animals corrects defects in dysregulated cellular functions and microbial clearance. The data on the role of lung collectins in immunomodulation are compelling, but the intracellular events by which they exert anti-inflammatory effects on activated immune cells are only partially understood. Deficiencies and inactivation of surfactant have been associated with a variety of human lung diseases in both infants and adults. In preterm infants, surfactant replacement therapies that include lipids and the hydrophobic surfactant proteins are highly efficacious in improving lung function. It is currently discussed that adult and infant patients suffering from diseases associated with lung infection may benefit from the anti-inflammatory and antimicrobial properties of the pulmonary collectins. Our group is investigating the functions and mechanisms of immune cells that are involved in the specific ability of pulmonary collectins to carry out immunomodulations that are important for preventing infection and inflammation. A better understanding of collectin-mediated lung immunity will contribute to the identification of disease states in which the therapeutic administration of pulmonary collectins may be beneficial.