Cellular Pneumology

Defense strategies that boost endogenous elements of innate lung responses to infection are a major focus both basic and translational to develop new prophylactic or therapeutic measures. The human C-type lectins surfactant protein (SP)-A and SP-D are soluble pattern recognition receptors regulating lung immune responses in vivo, partially by specifically controlling the high plasticity of alveolar macrophages towards lung immune homeostasis. We investigate lung specific innate imprinting by SP-A and SP-D to pulmonary infection with the focus on lung cell-specific/lectin interactions and downstream effects on cell activation/deactivation to target for development of therapeutic interventions.

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.

Deutsche Forschungsgemeinschaft (German Research Foundation)

• STA 609/2-1: "Pulmonary C-type lectin regulation of immune balance to bacterial lipopolysaccharide"
• MO 1999/2-1: "Endosomal signalling in innate immunity"

University of Lübeck

• Research Focus Biomedical Engineering

University Hospital Schleswig-Holstein

• CSSL - Connecting brain, metabolism and inflammation - mechanisms and disease expression

• collectin purification
• protein modification
• isolation of surfactant, in vitro surfactant function
• intratracheal infection models
• BAL cell isolation
• cell culture systems
• ELISA, EMSA, Western analysis
• immunoprecipitation
• RT-PCR
• transient transfection
• confocal microscopy

Head