Pulmonary Collectins Play Distinct Roles in Host Defense against Mycobacterium avium

Abstract

Pulmonary collectins, surfactant protein A (SP-A) and surfactant protein D (SP-D), play important roles in the innate immunity of the lung. Mycobacterium avium is one of the well-known opportunistic pathogens that can replicate within macrophages. We examined the effects of pulmonary collectins in host defense against M. avium infection achieved via direct interaction between bacteria and collectins. Although both pulmonary collectins bound to M. avium in a Ca2+-dependent manner, these collectins revealed distinct ligand-binding specificity and biological activities. SP-A and SP-D bound to a methoxy group containing lipid and lipoarabinomannan, respectively. Binding of SP-D but not SP-A resulted in agglutination of M. avium. A chimeric protein with the carbohydrate recognition domain of SP-D, which chimera revealed a bouquet-like arrangement similar to SP-A, also agglutinated M. avium. The ligand specificity of the carbohydrate recognition domain of SP-D seems to be necessary for agglutination activity. The binding of SP-A strongly inhibited the growth of M. avium in culture media. Although pulmonary collectins did not increase membrane permeability of M. avium, they attenuated the metabolic rate of the bacteria. Observations under a scanning electron microscope revealed that SP-A almost completely covers bacterial surfaces, whereas SP-D binds to certain areas like scattered dots. These observations suggest that a distinct binding pattern of collectins correlates with the difference of their biological activities. Furthermore, the number of bacteria phagocytosed by macrophages was significantly increased in the presence of SP-D. These data indicate that pulmonary collectins play critical roles in host defense against M. avium.

Surfactant protein D suppresses lung cancer progression by downregulation of epidermal growth factor signaling

“…3,4 For example, SP-D prevents dissemination of infectious microbes by their biological activities including agglutination and growth inhibition. [5][6][7] SP-D also promotes clearance of microbes by enhancing phagocytosis in macrophages. 8,9 In addition, SP-D interacts with the other pattern-recognition molecules including Toll-like receptors (TLRs) and TLR-associated molecules CD14 and MD-2, and regulates inflammatory responses.…”

Diverse Functions of Pulmonary Collectins in Host Defense of the Lung

“…Analysis of the crystal structure of SP-A reveals an extensive hydrophobic surface, which contributes to differences in binding specificity observed between this protein and SP-D [26]. When binding to Mycobacterium avium , SP-A binds lipid ligand on M. avium containing no saccharide, while SP-D binds mannose-rich glycolipid, lipoarabinomannan [27]. These findings suggest that SP-A tends to bind more to hydrophobic ligand than SP-D.…”

“…These data infer that pulmonary collectins inhibit the growth of M . avium by forming a physical barrier around the bacterial surface to restrict nutrient uptake [27]. …”

“…Furthermore, SP-A strongly inhibited the growth of M . avium in spite of its negligible agglutination activity against the bacteria [27]. Thus, it is likely that agglutination and growth inhibition by pulmonary collectins are independent activities.…”

Surfactant Protein D Inhibits Adherence of Uropathogenic Escherichia coli to the Bladder Epithelial Cells and the Bacterium-induced Cytotoxicity

“…A previous study has shown that O4-specific polysaccharides from E. coli O4:K6 are composed of D-glucose, L-rhamnose, 2-acetamido-2,6-dideoxy-L-galactose, and 2-acetamido-2-deoxy-D-glucose (36). On the other hand, SP-D binds lipoarabinomannan on M. tuberculosis and M. avium (37)(38)(39) and lipids on Mycoplasma pneumonia (40). O-antigen, a glycolipid, or a lipid on UPEC could be a candidate for an SP-D ligand.…”