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Departments of Medicine and Biochemistry, The Lawson Research Institute, St. Joseph’s Health Centre, The University of Western Ontario, London, Ontario, Canada;
Department of Pathology, Barnes Jewish Hospital of St. Louis, Washington University Medical Center, St. Louis, MO 63110 and
Department of Cell Biology, Duke University, Durham, NC 27710
Components of the airspace-lining material may contribute to the local regulation of immune function within the lung. We report here that recombinant rat pulmonary surfactant-associated protein D (SP-D) inhibits the lectin- and anti-CD3-stimulated proliferation of human PBMCs. Inhibition was associated with a decreased production of IL-2, and the addition of human rIL-2 blocked the inhibitory action of SP-D. These effects were not inhibited by maltose, indicating that the inhibitory activity was not dependent upon the lectin activity of SP-D. Studies employing mutant SP-D lacking N-linked sugars or defective in multimerization further indicated that inhibition was not dependent upon cellular interactions with the N-linked oligosaccharide on SP-D or the oligomerization of trimeric SP-D subunits. Although a peptide containing an inverted DGR showed similar IL-2-dependent effects on anti-CD3-stimulated proliferation, deletion of the conserved DGRDGR sequence near the amino-terminal end of the collagen domain did not decrease the suppressive activity of SP-D. We hypothesize that SP-D can dampen lymphocyte responses to exogenous stimuli and protect the lung against collateral immune-mediated damage.
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K. G. Brinker, E. Martin, P. Borron, E. Mostaghel, C. Doyle, C. V. Harding, and J. R. Wright Surfactant protein D enhances bacterial antigen presentation by bone marrow-derived dendritic cells Am J Physiol Lung Cell Mol Physiol, December 1, 2001; 281(6): L1453 - L1463. [Abstract] [Full Text] [PDF]
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S. Hawgood, J. Akiyama, C. Brown, L. Allen, G. Li, and F. R. Poulain GM-CSF mediates alveolar macrophage proliferation and type II cell hypertrophy in SP-D gene-targeted mice Am J Physiol Lung Cell Mol Physiol, June 1, 2001; 280(6): L1148 - L1156. [Abstract] [Full Text] [PDF]
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J. Madsen, A. Kliem, I. Tornoe, K. Skjodt, C. Koch, and U. Holmskov Localization of Lung Surfactant Protein D on Mucosal Surfaces in Human Tissues J. Immunol., June 1, 2000; 164(11): 5866 - 5870. [Abstract] [Full Text] [PDF]
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M. van Eijk, H. P. Haagsman, T. Skinner, A. Archibold, K. B. M. Reid, and P. R. Lawson Porcine Lung Surfactant Protein D: Complementary DNA Cloning, Chromosomal Localization, and Tissue Distribution J. Immunol., February 1, 2000; 164(3): 1442 - 1450. [Abstract] [Full Text] [PDF]
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 U. Holmskov, J. Mollenhauer, J. Madsen, L. Vitved, J. Gronlund, I. Tornoe, A. Kliem, K. B. M. Reid, A. Poustka, and K. Skjodt Cloning of gp-340, a putative opsonin receptor for lung surfactant protein D PNAS, September 14, 1999; 96(19): 10794 - 10799. [Abstract] [Full Text] [PDF]
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 L. Zhang, M. Ikegami, E. C. Crouch, T. R. Korfhagen, and J. A. Whitsett Activity of Pulmonary Surfactant Protein-D (SP-D) in Vivo Is Dependent on Oligomeric Structure J. Biol. Chem., May 25, 2001; 276(22): 19214 - 19219. [Abstract] [Full Text] [PDF]
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B. C. Trask, M. J. Malone, E. H. Lum, H. G. Welgus, E. C. Crouch, and S. D. Shapiro Induction of Macrophage Matrix Metalloproteinase Biosynthesis by Surfactant Protein D J. Biol. Chem., October 5, 2001; 276(41): 37846 - 37852. [Abstract] [Full Text] [PDF]
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