title: Surfactant protein A binds Mycoplasma pneumoniae with high affinity and attenuates its growth by recognition of disaturated phosphatidylglycerols.
abstract: Surfactant Protein A (SP-A) is an abundant, multifunctional lectin that resides within the bronchoalveolar compartment of the lung and plays an important role in the innate immunity of the organ. Mycoplasma pneumoniae is a human pathogen that resides in the same compartment as SP-A, and we examined the interaction between the two. Preparations of human and rat SP-A recognized the mycoplasma with high affinity in the presence of Ca(2+), exhibiting apparent K(')(d) values in the nanomolar range. Membranes prepared from the microbe also bound human and rat SP-A with similar characteristics and affinity to the intact cells. The ligand for SP-A was insensitive to proteolysis. Lipid extracts prepared from the mycoplasma, bound SP-A with high affinity when examined by ligand blot analysis. These lipid extracts were also potent competitive inhibitors (IC(50) = 0.2 nM) of human SP-A binding to mycoplasma membranes. The major lipid ligands for the protein identified by mass spectrometry are a group of disaturated phosphatidylglycerols. The addition of SP-A to cultures of M. pneumoniae markedly attenuated the growth of the organism assessed by colony formation, metabolic activity, and DNA replication. The bacteriostatic effects of SP-A were reversed by dipalmitoylphosphatidylglycerol. These findings demonstrate that human SP-A can play a direct role in antibody-independent immunity to M. pneumoniae by interacting with lipid ligands expressed on the surface of the organism and implicate SP-A in the immediate host response to the bacteria.
authors.affiliation: Program in Cell Biology, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
authors.forename: Surapon
authors.initials: S
authors.lastname: Piboonpocanun
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Chiba
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mitsuzawa
authors.forename: Wesley
authors.initials: W
authors.lastname: Martin
authors.forename: Robert C
authors.initials: RC
authors.lastname: Murphy
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Harbeck
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Voelker
mesh_terms: D000818:Animals; D006801:Humans; D007113:Immunity, Innate; D008024:Ligands; D009177:Mycoplasma pneumoniae / Q000254:growth & development / Q000378:metabolism*; D010715:Phosphatidylglycerols / Q000378:metabolism*; D011019:Pneumonia, Mycoplasma / Q000378:metabolism / Q000382:microbiology; D011485:Protein Binding; D037662:Pulmonary Surfactant-Associated Protein A / Q000276:immunology / Q000378:metabolism*; D051381:Rats
chemical_list: D008024:Ligands; D010715:Phosphatidylglycerols; D037662:Pulmonary Surfactant-Associated Protein A; C030345:1,2-dipalmitoylphosphatidylglycerol