P Borron, RA Veldhuizen, JF Lewis, F Possmayer, A Caveney, K Inchley, RG McFadden and LJ Fraher
Department of Medicine, Lawson Research Institute, St. Joseph's Health Centre, University of Western Ontario, London, Canada.

The hyporesponsive state of lung-derived mononuclear leukocytes has been, in part, attributed to the effects of the lipid rather than the protein components of pulmonary surfactant. In the present study, however, the results suggest that purified preparations of pulmonary surfactant-associated protein A (SP-A) suppress both phytohemagglutinin (PHA, 1 microgram/ml)- and anti-CD-3 (1 to 10 ng/ml) activated proliferation of human peripheral blood and tonsillar mononuclear cells in a dose-dependent manner at concentrations as low as 50 pM (6.25 micrograms/ml) when added at the initiation of cultures. Addition of SP- A to PHA-stimulated peripheral blood mononuclear cells (PBMC) as late as 24 to 36 h after PHA was also capable of suppressing [3H]thymidine incorporation measured at 72 h. In contrast, concanavalin A (Con A; 2 micrograms/ml)-stimulated PBMC proliferation was slightly augmented by the addition of SP-A. Analysis of the supernatants of PHA-stimulated cultures treated with SP-A revealed that accompanying the inhibition of proliferation was a corresponding decline in measurable interleukin-2 (IL-2) concentrations, from 154 pg/ml for the PHA-treated cells to 57.8, 28.4, 5.2, and less than 2 pg/ml of IL-2 when SP-A was added at 6.25, 12.5, 25, and 50 micrograms/ml, respectively. We suggest that the action of SP-A on PHA-stimulated human PBMC may involve the blocking of a costimulatory signal crucial for in vitro T-cell activation.

This article has been cited by other articles:

				B. Samten, J. C. Townsend, Z. Sever-Chroneos, V. Pasquinelli, P. F. Barnes, and Z. C. Chroneos An antibody against the surfactant protein A (SP-A)-binding domain of the SP-A receptor inhibits T cell-mediated immune responses to Mycobacterium tuberculosis J. Leukoc. Biol., July 1, 2008; 84(1): 115 - 123. [Abstract] [Full Text] [PDF]

				A. M. Pastva, J. R. Wright, and K. L. Williams Immunomodulatory Roles of Surfactant Proteins A and D: Implications in Lung Disease Proceedings of the ATS, July 1, 2007; 4(3): 252 - 257. [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]

				S. Kunzmann, J. R. Wright, W. Steinhilber, B. W. Kramer, K. Blaser, C. P. Speer, and C. Schmidt-Weber TGF-beta1 in SP-A preparations influence immune suppressive properties of SP-A on human CD4+ T lymphocytes Am J Physiol Lung Cell Mol Physiol, October 1, 2006; 291(4): L747 - L756. [Abstract] [Full Text] [PDF]

				D. C. Malherbe, V. J. Erpenbeck, S. N. Abraham, E. C. Crouch, J. M. Hohlfeld, and J. R. Wright Surfactant protein D decreases pollen-induced IgE-dependent mast cell degranulation Am J Physiol Lung Cell Mol Physiol, November 1, 2005; 289(5): L856 - L866. [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]

				B. Janic, T. M. Umstead, D. S. Phelps, and J. Floros Modulatory effects of ozone on THP-1 cells in response to SP-A stimulation Am J Physiol Lung Cell Mol Physiol, February 1, 2005; 288(2): L317 - L325. [Abstract] [Full Text] [PDF]

				T. C. Bailey, K. A. Da Silva, J. F. Lewis, K. Rodriguez-Capote, F. Possmayer, and R. A. W. Veldhuizen Physiological and inflammatory response to instillation of an oxidized surfactant in a rat model of surfactant deficiency J Appl Physiol, May 1, 2004; 96(5): 1674 - 1680. [Abstract] [Full Text] [PDF]

				W. Huang, G. Wang, D. S. Phelps, H. Al-Mondhiry, and J. Floros Human SP-A genetic variants and bleomycin-induced cytokine production by THP-1 cells: effect of ozone-induced SP-A oxidation Am J Physiol Lung Cell Mol Physiol, March 1, 2004; 286(3): L546 - L553. [Abstract] [Full Text] [PDF]

				D. S. Phelps, T. M. Umstead, M. Mejia, G. Carrillo, A. Pardo, and M. Selman Increased Surfactant Protein-A Levels in Patients With Newly Diagnosed Idiopathic Pulmonary Fibrosis Chest, February 1, 2004; 125(2): 617 - 625. [Abstract] [Full Text] [PDF]

				F. X. McCormack, R. Gibbons, S. R. Ward, A. Kuzmenko, H. Wu, and G. S. Deepe Jr. Macrophage-independent Fungicidal Action of the Pulmonary Collectins J. Biol. Chem., September 19, 2003; 278(38): 36250 - 36256. [Abstract] [Full Text] [PDF]

				S. Hussain, J. R. Wright, and W. J. Martin II Surfactant Protein A Decreases Nitric Oxide Production by Macrophages in a Tumor Necrosis Factor-{alpha}-Dependent Mechanism Am. J. Respir. Cell Mol. Biol., April 1, 2003; 28(4): 520 - 527. [Abstract] [Full Text] [PDF]

				K. G. Brinker, H. Garner, and J. R. Wright Surfactant protein A modulates the differentiation of murine bone marrow-derived dendritic cells Am J Physiol Lung Cell Mol Physiol, January 1, 2003; 284(1): L232 - L241. [Abstract] [Full Text] [PDF]

				P. J. Borron, E. A. Mostaghel, C. Doyle, E. S. Walsh, M. G. McHeyzer-Williams, and J. R. Wright Pulmonary Surfactant Proteins A and D Directly Suppress CD3+/CD4+ Cell Function: Evidence for Two Shared Mechanisms J. Immunol., November 15, 2002; 169(10): 5844 - 5850. [Abstract] [Full Text] [PDF]

				S. Yang, C. Milla, A. Panoskaltsis-Mortari, S. Hawgood, B. R. Blazar, and I. Y. Haddad Surfactant Protein A Decreases Lung Injury and Mortality after Murine Marrow Transplantation Am. J. Respir. Cell Mol. Biol., September 1, 2002; 27(3): 297 - 305. [Abstract] [Full Text] [PDF]

				A. M. LeVine, K. Hartshorn, J. Elliott, J. Whitsett, and T. Korfhagen Absence of SP-A modulates innate and adaptive defense responses to pulmonary influenza infection Am J Physiol Lung Cell Mol Physiol, March 1, 2002; 282(3): L563 - L572. [Abstract] [Full Text] [PDF]

				K. J. Haley, A. Ciota, J. P. Contreras, M. R. Boothby, D. L. Perkins, and P. W. Finn Alterations in lung collectins in an adaptive allergic immune response Am J Physiol Lung Cell Mol Physiol, March 1, 2002; 282(3): L573 - L584. [Abstract] [Full Text] [PDF]

				M. Johnson and S. Rennard Alternative Mechanisms for Long-Acting {beta}2-Adrenergic Agonists in COPD Chest, July 1, 2001; 120(1): 258 - 270. [Abstract] [Full Text] [PDF]

				J. R. Wright, P. Borron, K. G. Brinker, and R. J. Folz Surfactant Protein A . Regulation of Innate and Adaptive Immune Responses in Lung Inflammation Am. J. Respir. Cell Mol. Biol., May 1, 2001; 24(5): 513 - 517. [Full Text]

				T. W. Wright, R. H. Notter, Z. Wang, A. G. Harmsen, and F. Gigliotti Pulmonary Inflammation Disrupts Surfactant Function during Pneumocystis carinii Pneumonia Infect. Immun., February 1, 2001; 69(2): 758 - 764. [Abstract] [Full Text] [PDF]

				B. W. KRAMER, A. H. JOBE, C. J. BACHURSKI, and M. IKEGAMI Surfactant Protein A Recruits Neutrophils into the Lungs of Ventilated Preterm Lambs Am. J. Respir. Crit. Care Med., January 1, 2001; 163(1): 158 - 165. [Abstract] [Full Text]

				P. Borron, J. C. McIntosh, T. R. Korfhagen, J. A. Whitsett, J. Taylor, and J. R. Wright Surfactant-associated protein A inhibits LPS-induced cytokine and nitric oxide production in vivo Am J Physiol Lung Cell Mol Physiol, April 1, 2000; 278(4): L840 - L847. [Abstract] [Full Text] [PDF]

				S. Rosseau, P. Hammerl, U. Maus, A. Gunther, W. Seeger, F. Grimminger, and J. Lohmeyer Surfactant Protein A Down-Regulates Proinflammatory Cytokine Production Evoked by Candida albicans in Human Alveolar Macrophages and Monocytes J. Immunol., October 15, 1999; 163(8): 4495 - 4502. [Abstract] [Full Text] [PDF]

				R. Gagnon, J. Langridge, K. Inchley, J. Murotsuki, and F. Possmayer Changes in surfactant-associated protein mRNA profile in growth-restricted fetal sheep Am J Physiol Lung Cell Mol Physiol, March 1, 1999; 276(3): L459 - L465. [Abstract] [Full Text] [PDF]

				M. J. Tino and J. R. Wright Surfactant proteins A and D specifically stimulate directed actin-based responses in alveolar macrophages Am J Physiol Lung Cell Mol Physiol, January 1, 1999; 276(1): L164 - L174. [Abstract] [Full Text] [PDF]

				P. J. Borron, E. C. Crouch, J. F. Lewis, J. R. Wright, F. Possmayer, and L. J. Fraher Recombinant Rat Surfactant-Associated Protein D Inhibits Human T Lymphocyte Proliferation and IL-2 Production J. Immunol., November 1, 1998; 161(9): 4599 - 4603. [Abstract] [Full Text] [PDF]

				P. Borron, F. X. McCormack, B. M. Elhalwagi, Z. C. Chroneos, J. F. Lewis, S. Zhu, J. R. Wright, V. L. Shepherd, F. Possmayer, K. Inchley, et al. Surfactant protein A inhibits T cell proliferation via its collagen-like tail and a 210-kDa receptor Am J Physiol Lung Cell Mol Physiol, October 1, 1998; 275(4): L679 - L686. [Abstract] [Full Text] [PDF]

				E. C. Crouch Collectins and Pulmonary Host Defense Am. J. Respir. Cell Mol. Biol., August 1, 1998; 19(2): 177 - 201. [Abstract] [Full Text]

				J.-Y. WANG, C.-C. SHIEH, P.-F. YOU, H.-Y. LEI, and K. B. M. REID Inhibitory Effect of Pulmonary Surfactant Proteins A and D on Allergen-induced Lymphocyte Proliferation and Histamine Release in Children with Asthma Am. J. Respir. Crit. Care Med., August 1, 1998; 158(2): 510 - 518. [Abstract] [Full Text] [PDF]