No effect of ablation of surfactant protein-D on acute cerebral infarction in mice

Journal of Neuroinflammation

Bente Finsen⁵  Grith L Sorensen⁶  Pernille B Hansen⁶  Bjarne W Kristensen¹  Michael Meldgaard⁵  Stine B Thorsen⁴  Jan Stenvang⁴  Søren Hansen³  Bettina H Clausen⁵  Kamilla Østergaard²  Kate L Lambertsen⁵ 

[1] Department of Pathology, Odense University Hospital, DK-5000 Odense, Denmark;Department of Neurology, Odense University Hospital, DK-5000 Odense, Denmark;Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, DK-5000 Odense, Denmark;Institute of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2220 Copenhagen, Denmark;Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, JB Winsloewsvej 25, 2, DK-5000 Odense C, Denmark;Department of Cardiovascular and Renal Research, University of Southern Denmark, DK-5000 Odense, Denmark

关键词: Plasticity;    Phagocytosis;    Macrophages;    Microglia;    Tumor necrosis factor;    Collectins;    Middle cerebral artery occlusion;    Stroke;   

Others  :  1151342
DOI  :  10.1186/1742-2094-11-123

 received in 2014-01-12, accepted in 2014-07-03,  发布年份 2014

【 摘 要 】

Background

Crosstalk between the immune system in the brain and the periphery may contribute to the long-term outcome both in experimental and clinical stroke. Although, the immune defense collectin surfactant protein-D (SP-D) is best known for its role in pulmonary innate immunity, SP-D is also known to be involved in extrapulmonary modulation of inflammation in mice. We investigated whether SP-D affected cerebral ischemic infarction and ischemia-induced inflammatory responses in mice.

Methods

The effect of SP-D was studied by comparing the size of ischemic infarction and the inflammatory and astroglial responses in SP-D knock out (KO) and wild type (WT) mice subjected to permanent middle cerebral artery occlusion. SP-D mRNA production was assessed in isolated cerebral arteries and in the whole brain by PCR, and SP-D protein in normal appearing and ischemic human brain by immunohistochemistry. Changes in plasma SP-D and TNF were assessed by ELISA and proximity ligation assay, respectively.

Results

Infarct volumetric analysis showed that ablation of SP-D had no effect on ischemic infarction one and five days after induction of ischemia. Further, ablation of SP-D had no effect on the ischemia-induced increase in TNF mRNA production one day after induction of ischemia; however the TNF response to the ischemic insult was affected at five days. SP-D mRNA was not detected in parenchymal brain cells in either naïve mice or in mice subjected to focal cerebral ischemia. However, SP-D mRNA was detected in middle cerebral artery cells in WT mice and SP-D protein in vascular cells both in normal appearing and ischemic human brain tissue. Measurements of the levels of SP-D and TNF in plasma in mice suggested that levels were unaffected by the ischemic insult. Microglial-leukocyte and astroglial responses were comparable in SP-D KO and WT mice.

Conclusions

SP-D synthesis in middle cerebral artery cells is consistent with SP-D conceivably leaking into the infarcted area and affecting local cytokine production. However, there was no SP-D synthesis in parenchymal brain cells and ablation of SP-D had no effect on ischemic cerebral infarction.

【 授权许可】

   
2014 Lambertsen et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Wert SE, Yoshida M, LeVine AM, Ikegami M, Jones T, Ross GF, Fisher JH, Korfhagen TR, Whitsett JA: Increased metalloproteinase activity, oxidant production, and emphysema in surfactant protein D gene-inactivated mice. Proc Natl Acad Sci U S A 2000, 97:5972-5977.
• [2]Ofek I, Mesika A, Kalina M, Keisari Y, Podschun R, Sahly H, Chang D, McGregor D, Crouch E: Surfactant protein D enhances phagocytosis and killing of unencapsulated phase variants of Klebsiella pneumoniae. Infect Immun 2001, 69:24-33.
• [3]Wright JR: Immunoregulatory functions of surfactant proteins. Nat Rev Immunol 2005, 5:58-68.
• [4]Ohya M, Nishitani C, Sano H, Yamada C, Mitsuzawa H, Shimizu T, Saito T, Smith K, Crouch E, Kuroki Y: Human pulmonary surfactant protein D binds the extracellular domains of Toll-like receptors 2 and 4 through the carbohydrate recognition domain by a mechanism different from its binding to phosphatidylinositol and lipopolysaccharide. Biochemistry 2006, 45:8657-8664.
• [5]Liu CF, Rivere M, Huang HJ, Puzo G, Wang JY: Surfactant protein D inhibits mite-induced alveolar macrophage and dendritic cell activations through TLR signalling and DC-SIGN expression. Clinical Exp Allergy J British Soc Allergy Clinical Immunol 2010, 40:111-122.
• [6]Yoshida M, Korfhagen TR, Whitsett JA: Surfactant protein D regulates NF-kappa B and matrix metalloproteinase production in alveolar macrophages via oxidant-sensitive pathways. J Immunol 2001, 166:7514-7519.
• [7]LeVine AM, Whitsett JA, Gwozdz JA, Richardson TR, Fisher JH, Burhans MS, Korfhagen TR: Distinct effects of surfactant protein A or D deficiency during bacterial infection on the lung. J Immunol 2000, 165:3934-3940.
• [8]Fujita M, Shannon JM, Ouchi H, Voelker DR, Nakanishi Y, Mason RJ: Serum surfactant protein D is increased in acute and chronic inflammation in mice. Cytokine 2005, 31:25-33.
• [9]Sorensen GL, Madsen J, Kejling K, Tornoe I, Nielsen O, Townsend P, Poulain F, Nielsen CH, Reid KB, Hawgood S, Falk E, Holmskov U: Surfactant protein D is proatherogenic in mice. Am J Physiol Heart Circ Physiol 2006, 290:H2286-H2294.
• [10]Madsen J, Kliem A, Tornoe I, Skjodt K, Koch C, Holmskov U: Localization of lung surfactant protein D on mucosal surfaces in human tissues. J Immunol 2000, 164:5866-5870.
• [11]Snyder GD, Oberley-Deegan RE, Goss KL, Romig-Martin SA, Stoll LL, Snyder JM, Weintraub NL: Surfactant protein D is expressed and modulates inflammatory responses in human coronary artery smooth muscle cells. Am J Physiol Heart Circ Physiol 2008, 294:H2053-H2059.
• [12]Lee MY, Sorensen GL, Holmskov U, Vanhoutte PM: The presence and activity of SP-D in porcine coronary endothelial cells depend on Akt/PI3K, Erk and nitric oxide and decrease after multiple passaging. Mol Immunol 2009, 46:1050-1057.
• [13]Mocco J, Mack WJ, Ducruet AF, Sosunov SA, Sughrue ME, Hassid BG, Nair MN, Laufer I, Komotar RJ, Claire M, Holland H, Pinsky DJ, Connolly ES Jr: Complement component C3 mediates inflammatory injury following focal cerebral ischemia. Circ Res 2006, 99:209-217.
• [14]Veerhuis R, Nielsen HM, Tenner AJ: Complement in the brain. Mol Immunol 2011, 48:1592-1603.
• [15]Yanamadala V, Friedlander RM: Complement in neuroprotection and neurodegeneration. Trends Mol Med 2010, 16:69-76.
• [16]Orsini F, Villa P, Parrella S, Zangari R, Zanier ER, Gesuete R, Stravalaci M, Fumagalli S, Ottria R, Reina JJ, Paladini A, Micotti E, Ribeiro-Viana R, Rojo J, Pavlov VI, Stahl GL, Bernardi A, Gobbi M, De Simoni MG: Targeting mannose-binding lectin confers long-lasting protection with a surprisingly wide therapeutic window in cerebral ischemia. Circulation 2012, 126:1484-1494.
• [17]Osthoff M, Katan M, Fluri F, Schuetz P, Bingisser R, Kappos L, Steck AJ, Engelter ST, Mueller B, Christ-Crain M, Trendelenburg M: Mannose-binding lectin deficiency is associated with smaller infarction size and favorable outcome in ischemic stroke patients. PLoS One 2011, 6:e21338.
• [18]Cervera A, Planas AM, Justicia C, Urra X, Jensenius JC, Torres F, Lozano F, Chamorro A: Genetically-defined deficiency of mannose-binding lectin is associated with protection after experimental stroke in mice and outcome in human stroke. PLoS One 2010, 5:e8433.
• [19]Nybo M, Andersen K, Sorensen GL, Lolk A, Kragh-Sorensen P, Holmskov U: Serum surfactant protein D is correlated to development of dementia and augmented mortality. Clin Immunol 2007, 123:333-337.
• [20]Tu XK, Yang WZ, Shi SS, Wang CH, Zhang GL, Ni TR, Chen CM, Wang R, Jia JW, Song QM: Spatio-temporal distribution of inflammatory reaction and expression of TLR2/4 signaling pathway in rat brain following permanent focal cerebral ischemia. Neurochem Res 2010, 35:1147-1155.
• [21]Janssen WJ, McPhillips KA, Dickinson MG, Linderman DJ, Morimoto K, Xiao YQ, Oldham KM, Vandivier RW, Henson PM, Gardai SJ: Surfactant proteins A and D suppress alveolar macrophage phagocytosis via interaction with SIRP alpha. Am J Respir Crit Care Med 2008, 178:158-167.
• [22]Gardai SJ, Xiao YQ, Dickinson M, Nick JA, Voelker DR, Greene KE, Henson PM: By binding SIRPalpha or calreticulin/CD91, lung collectins act as dual function surveillance molecules to suppress or enhance inflammation. Cell 2003, 115:13-23.
• [23]Wang L, Lu Y, Deng S, Zhang Y, Yang L, Guan Y, Matozaki T, Ohnishi H, Jiang H, Li H: SHPS-1 deficiency induces robust neuroprotection against experimental stroke by attenuating oxidative stress. J Neurochem 2012, 122:834-843.
• [24]Botas C, Poulain F, Akiyama J, Brown C, Allen L, Goerke J, Clements J, Carlson E, Gillespie AM, Epstein C, Hawgood S: Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein D. Proc Natl Acad Sci U S A 1998, 95:11869-11874.
• [25]Sorensen GL, Hjelmborg JB, Kyvik KO, Fenger M, Hoj A, Bendixen C, Sorensen TI, Holmskov U: Genetic and environmental influences of surfactant protein D serum levels. Am J Physiol Lung Cell Mol Physiol 2006, 290:L1010-L1017.
• [26]Gregersen R, Lambertsen K, Finsen B: Microglia and macrophages are the major source of tumor necrosis factor in permanent middle cerebral artery occlusion in mice. J Cereb Blood Flow Metab 2000, 20:53-65.
• [27]Lambertsen KL, Gregersen R, Drojdahl N, Owens T, Finsen B: A specific and sensitive method for visualization of tumor necrosis factor in the murine central nervous system. Brain Res Brain Res Protoc 2001, 7:175-191.
• [28]Moller HE, Gaupp A, Vestring T, Dietl KH, Vermathen P, Buchholz B, Peters PE: Kinetics of metabolism in human kidney transplants measured by dynamic 31P NMR spectroscopy. Z Naturforsch C 1995, 50:439-450.
• [29]Lin TN, He YY, Wu G, Khan M, Hsu CY: Effect of brain edema on infarct volume in a focal cerebral ischemia model in rats. Stroke J Cereb Circulat 1993, 24:117-121.
• [30]Lambertsen KL, Clausen BH, Babcock AA, Gregersen R, Fenger C, Nielsen HH, Haugaard LS, Wirenfeldt M, Nielsen M, Dagnaes-Hansen F, Bluethmann H, Faergeman NJ, Meldgaard M, Deierborg T, Finsen B: Microglia protect neurons against ischemia by synthesis of tumor necrosis factor. J Neurosci 2009, 29:1319-1330.
• [31]Clausen BH, Lambertsen KL, Babcock AA, Holm TH, Dagnaes-Hansen F, Finsen B: Interleukin-1beta and tumor necrosis factor-alpha are expressed by different subsets of microglia and macrophages after ischemic stroke in mice. J Neuroinflammation 2008, 5:46. BioMed Central Full Text
• [32]Meldgaard M, Fenger C, Lambertsen KL, Pedersen MD, Ladeby R, Finsen B: Validation of two reference genes for mRNA level studies of murine disease models in neurobiology. J Neurosci Methods 2006, 156:101-110.
• [33]Dissing-Olesen L, Thaysen-Andersen M, Meldgaard M, Hojrup P, Finsen B: The function of the human interferon-beta 1a glycan determined in vivo. J Pharmacol Exp Ther 2008, 326:338-347.
• [34]Clausen BH, Lambertsen KL, Meldgaard M, Finsen B: A quantitative in situ hybridization and polymerase chain reaction study of microglial-macrophage expression of interleukin-1beta mRNA following permanent middle cerebral artery occlusion in mice. Neuroscience 2005, 132:879-892.
• [35]Hansen S, Schmidt V, Steffensen MA, Jensen PH, Gjerstorff M, Thiel S, Holmskov U: An enzyme-linked immunosorbent assay (ELISA) for quantification of mouse surfactant protein D (SP-D). J Immunol Methods 2008, 330:75-85.
• [36]Campanella M, Sciorati C, Tarozzo G, Beltramo M: Flow cytometric analysis of inflammatory cells in ischemic rat brain. Stroke 2002, 33:586-592.
• [37]Zehntner SP, Brickman C, Bourbonniere L, Remington L, Caruso M, Owens T: Neutrophils that infiltrate the central nervous system regulate T cell responses. J Immunol 2005, 174:5124-5131.
• [38]Lundberg M, Eriksson A, Tran B, Assarsson E, Fredriksson S: Homogeneous antibody-based proximity extension assays provide sensitive and specific detection of low-abundant proteins in human blood. Nucleic Acids Res 2011, 39:e102.
• [39]Brambilla R, Couch Y, Lambertsen KL: The effect of stroke on immune function. Mol Cell Neurosci 2013, 53:26-33.
• [40]Macrez R, Ali C, Toutirais O, Le Mauff B, Defer G, Dirnagl U, Vivien D: Stroke and the immune system: from pathophysiology to new therapeutic strategies. Lancet Neurol 2011, 10:471-480.
• [41]Clark H, Palaniyar N, Strong P, Edmondson J, Hawgood S, Reid KB: Surfactant protein D reduces alveolar macrophage apoptosis in vivo. J Immunol 2002, 169:2892-2899.
• [42]Motwani M, White RA, Guo N, Dowler LL, Tauber AI, Sastry KN: Mouse surfactant protein-D. cDNA cloning, characterization, and gene localization to chromosome 14. J Immunol 1995, 155:5671-5677.
• [43]Persson L, Hardemark HG, Bolander HG, Hillered L, Olsson Y: Neurologic and neuropathologic outcome after middle cerebral artery occlusion in rats. Stroke 1989, 20:641-645.
• [44]Lambertsen KL, Meldgaard M, Ladeby R, Finsen B: A quantitative study of microglial-macrophage synthesis of tumor necrosis factor during acute and late focal cerebral ischemia in mice. J Cereb Blood Flow Metab 2005, 25:119-135.
• [45]Krakauer JW, Carmichael ST, Corbett D, Wittenberg GF: Getting neurorehabilitation right: what can be learned from animal models? Neurorehabil Neural Repair 2012, 26:923-931.
• [46]Lambertsen KL, Biber K, Finsen B: Inflammatory cytokines in experimental and human stroke. J Cereb Blood Flow Metab 2012, 32:1677-1698.
• [47]Sorensen GL, Husby S, Holmskov U: Surfactant protein A and surfactant protein D variation in pulmonary disease. Immunobiology 2007, 212:381-416.
• [48]Gaunsbaek MQ, Rasmussen KJ, Beers MF, Atochina-Vasserman EN, Hansen S: Lung surfactant protein D (SP-D) response and regulation during acute and chronic lung injury. Lung 2013, 191:295-303.
• [49]Inacio AR, Bucala R, Deierborg T: Lack of macrophage migration inhibitory factor in mice does not affect hallmarks of the inflammatory/immune response during the first week after stroke. J Neuroinflammation 2011, 8:75. BioMed Central Full Text