Protective role of the lung collectins surfactant protein A and surfactant protein D in airway inflammation.
The acute inflammatory airway response is characterized by a time-dependent onset followed by active resolution. Emerging evidence suggests that epithelial cells of the proximal and distal air spaces release host defense mediators that can facilitate both the initiation and the resolution part of inflammatory airway changes. These molecules, also known as the hydrophilic surfactant proteins (surfactant protein [SP]-A and SP-D) belong to the class of collagenous lectins (collectins). The collectins are a small family of soluble pattern recognition receptors containing collagenous regions and C-type lectin domains. SP-A and SP-D are most abundant in the lung. Because of their structural uniqueness, specific localization, and functional versatility, lung collectins are important players of the pulmonary immune responses. Recent studies in our laboratory and others indicated significant associations of lung collectin levels with acute and chronic airway inflammation in both animal models and patients, suggesting the usefulness of these molecules as disease biomarkers. Research on wild-type and mutant recombinant molecules in vivo and in vitro showed that SP-A and SP-D bind carbohydrates, lipids, and nucleic acids with a broad-spectrum specificity and initiate phagocytosis of inhaled pathogens as well as apoptotic cells. Investigations on gene-deficient and conditional overexpresser mice indicated that lung collectins also directly modulate innate immune cell function and T-cell-dependent inflammatory events. Thus, these molecules have a unique, dual-function capacity to induce pathogen elimination and control proinflammatory mechanisms, suggesting a potential suitability for therapeutic prevention and treatment of chronic airway inflammation. This article reviews evidence supporting that the lung collectins play an immune-protective role and are essential for maintenance of the immunologic homeostasis in the lung.
Haczku
Angela
A
Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA. haczku@mail.med.upenn.edu
D000818:Animals; D037222:Collectins / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008168:Lung / Q000276:immunology; D011110:Polymorphism, Genetic; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000276:immunology*; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology*
D037222:Collectins; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D