|
|
||||||||


* Veterans Affairs Medical Center and Division of Infectious Diseases, Departments of Medicine and Microbiology, Interdisciplinary Immunology Program, University of Iowa, Iowa City, IA 52242;
Lord and Taylor Laboratory for Lung Biochemistry, Program in Cell Biology, Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine and Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80206;
Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Cincinnati, Cincinnati, OH 45267
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.
This article has been cited by other articles:
![]() |
A. K. Azad, J. B. Torrelles, and L. S. Schlesinger Mutation in the DC-SIGN cytoplasmic triacidic cluster motif markedly attenuates receptor activity for phagocytosis and endocytosis of mannose-containing ligands by human myeloid cells J. Leukoc. Biol., December 1, 2008; 84(6): 1594 - 1603. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Hodge, G. Hodge, H. Jersmann, G. Matthews, J. Ahern, M. Holmes, and P. N. Reynolds Azithromycin Improves Macrophage Phagocytic Function and Expression of Mannose Receptor in Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., July 15, 2008; 178(2): 139 - 148. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. N. Henning, A. K. Azad, K. V. L. Parsa, J. E. Crowther, S. Tridandapani, and L. S. Schlesinger Pulmonary Surfactant Protein A Regulates TLR Expression and Activity in Human Macrophages J. Immunol., June 15, 2008; 180(12): 7847 - 7858. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. P. Senft, T. R. Korfhagen, J. A. Whitsett, and A. M. LeVine Surfactant protein D regulates the cell surface expression of alveolar macrophage beta2-integrins Am J Physiol Lung Cell Mol Physiol, February 1, 2007; 292(2): L469 - L475. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. S. Ferguson, J. L. Martin, A. K. Azad, T. R. McCarthy, P. B. Kang, D. R. Voelker, E. C. Crouch, and L. S. Schlesinger Surfactant Protein D Increases Fusion of Mycobacterium tuberculosis- Containing Phagosomes with Lysosomes in Human Macrophages Infect. Immun., December 1, 2006; 74(12): 7005 - 7009. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Ono, C. Nishitani, H. Mitsuzawa, T. Shimizu, H. Sano, H. Suzuki, T. Kodama, N. Fujii, K. Fukase, K. Hirata, et al. Mannose-Binding Lectin Augments the Uptake of Lipid A, Staphylococcus aureus, and Escherichia coli by Kupffer Cells through Increased Cell Surface Expression of Scavenger Receptor A J. Immunol., October 15, 2006; 177(8): 5517 - 5523. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Balagopal, A. S. MacFarlane, N. Mohapatra, S. Soni, J. S. Gunn, and L. S. Schlesinger Characterization of the Receptor-Ligand Pathways Important for Entry and Survival of Francisella tularensis in Human Macrophages Infect. Immun., September 1, 2006; 74(9): 5114 - 5125. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Hall-Stoodley, G. Watts, J. E. Crowther, A. Balagopal, J. B. Torrelles, J. Robison-Cox, R. F. Bargatze, A. G. Harmsen, E. C. Crouch, and L. S. Schlesinger Mycobacterium tuberculosis Binding to Human Surfactant Proteins A and D, Fibronectin, and Small Airway Epithelial Cells under Shear Conditions. Infect. Immun., June 1, 2006; 74(6): 3587 - 3596. [Abstract] [Full Text] [PDF] |
||||
![]() |
C.-H. Yang, J. Szeliga, J. Jordan, S. Faske, Z. Sever-Chroneos, B. Dorsett, R. E. Christian, R. E. Settlage, J. Shabanowitz, D. F. Hunt, et al. Identification of the Surfactant Protein A Receptor 210 as the Unconventional Myosin 18A J. Biol. Chem., October 14, 2005; 280(41): 34447 - 34457. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. A. Beharka, J. E. Crowther, F. X. McCormack, G. M. Denning, J. Lees, E. Tibesar, and L. S. Schlesinger Pulmonary Surfactant Protein A Activates a Phosphatidylinositol 3-Kinase/Calcium Signal Transduction Pathway in Human Macrophages: Participation in the Up-Regulation of Mannose Receptor Activity J. Immunol., August 15, 2005; 175(4): 2227 - 2236. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Hawgood, C. Brown, J. Edmondson, A. Stumbaugh, L. Allen, J. Goerke, H. Clark, and F. Poulain Pulmonary Collectins Modulate Strain-Specific Influenza A Virus Infection and Host Responses J. Virol., August 15, 2004; 78(16): 8565 - 8572. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. E. Oberley, K. A. Ault, T. L. Neff, K. R. Khubchandani, E. C. Crouch, and J. M. Snyder Surfactant proteins A and D enhance the phagocytosis of Chlamydia into THP-1 cells Am J Physiol Lung Cell Mol Physiol, August 1, 2004; 287(2): L296 - L306. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Kudo, H. Sano#, H. Takahashi, K. Kuronuma, S.-i. Yokota, N. Fujii, K.-i. Shimada, I. Yano, Y. Kumazawa, D. R. Voelker, et al. Pulmonary Collectins Enhance Phagocytosis of Mycobacterium avium through Increased Activity of Mannose Receptor J. Immunol., June 15, 2004; 172(12): 7592 - 7602. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. E. Crowther, V. K. Kutala, P. Kuppusamy, J. S. Ferguson, A. A. Beharka, J. L. Zweier, F. X. McCormack, and L. S. Schlesinger Pulmonary Surfactant Protein A Inhibits Macrophage Reactive Oxygen Intermediate Production in Response to Stimuli by Reducing NADPH Oxidase Activity J. Immunol., June 1, 2004; 172(11): 6866 - 6874. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |