title: Pulmonary surfactant protein A up-regulates activity of the mannose receptor, a pattern recognition receptor expressed on human macrophages.
abstract: Inhaled particulates and microbes are continually cleared by a complex array of lung innate immune determinants, including alveolar macrophages (AMs). AMs are unique cells with an enhanced capacity for phagocytosis that is due, in part, to increased activity of the macrophage mannose receptor (MR), a pattern recognition receptor for various microorganisms. The local factors that "shape" AM function are not well understood. Surfactant protein A (SP-A), a major component of lung surfactant, participates in the innate immune response and can enhance phagocytosis. Here we show that SP-A selectively enhances MR expression on human monocyte-derived macrophages, a process involving both the attached sugars and collagen-like domain of SP-A. The newly expressed MR is functional. Monocyte-derived macrophages on an SP-A substrate demonstrated enhanced pinocytosis of mannose BSA and phagocytosis of Mycobacterium tuberculosis lipoarabinomannan-coated microspheres. The newly expressed MR likely came from intracellular pools because: 1) up-regulation of the MR by SP-A occurred by 1 h, 2) new protein synthesis was not necessary for MR up-regulation, and 3) pinocytosis of mannose BSA via MR recycling was increased. AMs from SP-A(-/-) mice have reduced MR expression relative to SP-A(+/+). SP-A up-regulation of MR activity provides a mechanism for enhanced phagocytosis of microbes by AMs, thereby enhancing lung host defense against extracellular pathogens or, paradoxically, enhancing the potential for intracellular pathogens to enter their intracellular niche. SP-A contributes to the alternative activation state of the AM in the lung.
authors.affiliation: Veterans Affairs Medical Center and Division of Infectious Diseases, Department of Medicine and Microbiology, Interdisciplinary Immunology Program, University of Iowa, Iowa City, IA 52242, USA. hiroyuki.matsue@utsouthwestern.edu
authors.forename: Alison A
authors.initials: AA
authors.lastname: Beharka
authors.forename: Cecilia D
authors.initials: CD
authors.lastname: Gaynor
authors.forename: Byoung K
authors.initials: BK
authors.lastname: Kang
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Voelker
authors.forename: Francis X
authors.initials: FX
authors.lastname: McCormack
authors.forename: Larry S
authors.initials: LS
authors.lastname: Schlesinger
mesh_terms: D000276:Adjuvants, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000502:physiology; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D037181:Lectins, C-Type; D008070:Lipopolysaccharides / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008358:Mannose / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D051379:Mice; D018345:Mice, Knockout; D008863:Microspheres; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009844:Oligosaccharides / Q000502:physiology; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D017434:Protein Structure, Tertiary / Q000235:genetics; D037662:Pulmonary Surfactant-Associated Protein A / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D007457:Iodine Radioisotopes; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009844:Oligosaccharides; D037662:Pulmonary Surfactant-Associated Protein A; D011956:Receptors, Cell Surface; D012709:Serum Albumin; C050016:lipoarabinomannan; C023840:mannose-bovine serum albumin conjugate; D003094:Collagen; D008358:Mannose