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DOI: 10.1055/s-0038-1669477
Macrophagic Stabilin-1 Restored Disruption of Vascular Integrity Caused by Sepsis
Funding This research study was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Government of the Republic of Korea (grant number: HI15C0001), by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (2017M3A9G8083382), by the National Research Foundation of Korea (NRF) grant funded by the Korean government (NRF-2017R1A5A2015391) and by the Korean government (Ministry of Science, ICT) and the Korea Research Institute of Bioscience and Biotechnology Research Initiative Program (KGM3141824).Publication History
12 April 2018
18 July 2018
Publication Date:
20 September 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/201810/lookinside/thumbnails/10-1055-s-0038-1669477_180274-1.jpg)
Abstract
Sepsis develops because of overwhelming inflammatory responses to bacterial infection, and disrupts vascular integrity. Stabilin-1 (STAB-1) is a phagocytic receptor, which mediates efferocytosis in a phosphatidylserine (PS)-dependent manner. STAB-1 is expected to play important roles in efferocytosis during sepsis. Here, we determined the role of STAB-1 in maintaining and restoring vascular integrity. Macrophages and vascular endothelial cells were used to assess the effect of STAB-1 on survival rate, phagocytic activity, vascular permeability and transendothelial migration (TEM). Additionally, we investigated whether the high-mobility group box 1 (HMGB1)-receptor for advanced glycated end products complex interfered with the binding of Stab1 to PS. Mortality rate was higher in the Stab1-knockout mice than in the wild-type mice, and STAB-1 deficiency was related to reduced macrophage-mediated efferocytosis and the disruption of vascular integrity, which increased vascular permeability, and enhanced TEM. STAB-1 deficiency promoted lung injury, and elevated the expression of sepsis markers. The exogenous application of the anti-HMGB1 neutralizing antibody improved efferocytosis, vascular integrity and survival rate in sepsis. Collectively, our findings indicated that STAB-1 regulated and maintained vascular integrity through the clearance of infected apoptotic endothelial cells. Moreover, our results suggested that interventions targeting vascular integrity by STAB-1 signalling are promising therapeutic approaches to sepsis.
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References
- 1 Gustot T. Multiple organ failure in sepsis: prognosis and role of systemic inflammatory response. Curr Opin Crit Care 2011; 17 (02) 153-159
- 2 Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med 2013; 369 (09) 840-851
- 3 Kellum JA. Metabolic acidosis in patients with sepsis: epiphenomenon or part of the pathophysiology?. Crit Care Resusc 2004; 6 (03) 197-203
- 4 Bogatcheva NV, Verin AD. The role of cytoskeleton in the regulation of vascular endothelial barrier function. Microvasc Res 2008; 76 (03) 202-207
- 5 Gupta S, Agrawal A, Agrawal S, Su H, Gollapudi S. A paradox of immunodeficiency and inflammation in human aging: lessons learned from apoptosis. Immun Ageing 2006; 3: 5
- 6 Botto M, Dell'Agnola C, Bygrave AE. , et al. Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat Genet 1998; 19 (01) 56-59
- 7 Douglas IS, Diaz del Valle F, Winn RA, Voelkel NF. Beta-catenin in the fibroproliferative response to acute lung injury. Am J Respir Cell Mol Biol 2006; 34 (03) 274-285
- 8 Henson PM, Cosgrove GP, Vandivier RW. State of the art. Apoptosis and cell homeostasis in chronic obstructive pulmonary disease. Proc Am Thorac Soc 2006; 3 (06) 512-516
- 9 Ravichandran KS, Lorenz U. Engulfment of apoptotic cells: signals for a good meal. Nat Rev Immunol 2007; 7 (12) 964-974
- 10 Savill J, Dransfield I, Gregory C, Haslett C. A blast from the past: clearance of apoptotic cells regulates immune responses. Nat Rev Immunol 2002; 2 (12) 965-975
- 11 Kzhyshkowska J, Gratchev A, Goerdt S. Stabilin-1, a homeostatic scavenger receptor with multiple functions. J Cell Mol Med 2006; 10 (03) 635-649
- 12 Goerdt S, Bhardwaj R, Sorg C. Inducible expression of MS-1 high-molecular-weight protein by endothelial cells of continuous origin and by dendritic cells/macrophages in vivo and in vitro. Am J Pathol 1993; 142 (05) 1409-1422
- 13 Politz O, Gratchev A, McCourt PA. , et al. Stabilin-1 and -2 constitute a novel family of fasciclin-like hyaluronan receptor homologues. Biochem J 2002; 362 (Pt 1): 155-164
- 14 Adachi H, Tsujimoto M. FEEL-1, a novel scavenger receptor with in vitro bacteria-binding and angiogenesis-modulating activities. J Biol Chem 2002; 277 (37) 34264-34270
- 15 Tamura Y, Adachi H, Osuga J. , et al. FEEL-1 and FEEL-2 are endocytic receptors for advanced glycation end products. J Biol Chem 2003; 278 (15) 12613-12617
- 16 Park SY, Jung MY, Lee SJ. , et al. Stabilin-1 mediates phosphatidylserine-dependent clearance of cell corpses in alternatively activated macrophages. J Cell Sci 2009; 122 (Pt 18): 3365-3373
- 17 Park SY, Bae DJ, Kim MJ, Piao ML, Kim IS. Extracellular low pH modulates phosphatidylserine-dependent phagocytosis in macrophages by increasing stabilin-1 expression. J Biol Chem 2012; 287 (14) 11261-11271
- 18 Rodríguez CI, Buchholz F, Galloway J. , et al. High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP. Nat Genet 2000; 25 (02) 139-140
- 19 O'Gorman S, Dagenais NA, Qian M, Marchuk Y. Protamine-Cre recombinase transgenes efficiently recombine target sequences in the male germ line of mice, but not in embryonic stem cells. Proc Natl Acad Sci U S A 1997; 94 (26) 14602-14607
- 20 Bone RC, Balk RA, Cerra FB. , et al; The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest 1992; 101 (06) 1644-1655
- 21 Bone RC, Sibbald WJ, Sprung CL. The ACCP-SCCM consensus conference on sepsis and organ failure. Chest 1992; 101 (06) 1481-1483
- 22 Sallusto F, Lanzavecchia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med 1994; 179 (04) 1109-1118
- 23 Verreck FA, de Boer T, Langenberg DM. , et al. Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco)bacteria. Proc Natl Acad Sci U S A 2004; 101 (13) 4560-4565
- 24 Lee SJ, Park SY, Jung MY, Bae SM, Kim IS. Mechanism for phosphatidylserine-dependent erythrophagocytosis in mouse liver. Blood 2011; 117 (19) 5215-5223
- 25 Ding AH, Nathan CF, Stuehr DJ. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J Immunol 1988; 141 (07) 2407-2412
- 26 Albina JE, Cui S, Mateo RB, Reichner JS. Nitric oxide-mediated apoptosis in murine peritoneal macrophages. J Immunol 1993; 150 (11) 5080-5085
- 27 Yoon EK, Ku SK, Lee W. , et al. Antitcoagulant and antiplatelet activities of scolymoside. BMB Rep 2015; 48 (10) 577-582
- 28 Lee W, Seo J, Kwak S. , et al. A double-chambered protein nanocage loaded with thrombin receptor agonist peptide (TRAP) and γ-carboxyglutamic acid of protein C (PC-Gla) for sepsis treatment. Adv Mater 2015; 27 (42) 6637-6643
- 29 Lawrence T, Natoli G. Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat Rev Immunol 2011; 11 (11) 750-761
- 30 Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci 2009; 29 (43) 13435-13444
- 31 García A, Serrano A, Abril E. , et al. Differential effect on U937 cell differentiation by targeting transcriptional factors implicated in tissue- or stage-specific induced integrin expression. Exp Hematol 1999; 27 (02) 353-364
- 32 Rittirsch D, Huber-Lang MS, Flierl MA, Ward PA. Immunodesign of experimental sepsis by cecal ligation and puncture. Nat Protoc 2009; 4 (01) 31-36
- 33 Wang H, Liao H, Ochani M. , et al. Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med 2004; 10 (11) 1216-1221
- 34 Akeson AL, Woods CW. A fluorometric assay for the quantitation of cell adherence to endothelial cells. J Immunol Methods 1993; 163 (02) 181-185
- 35 Kim TH, Ku SK, Lee IC, Bae JS. Anti-inflammatory functions of purpurogallin in LPS-activated human endothelial cells. BMB Rep 2012; 45 (03) 200-205
- 36 Bae JS, Lee W, Rezaie AR. Polyphosphate elicits pro-inflammatory responses that are counteracted by activated protein C in both cellular and animal models. J Thromb Haemost 2012; 10 (06) 1145-1151
- 37 Lee JD, Huh JE, Jeon G. , et al. Flavonol-rich RVHxR from Rhus verniciflua Stokes and its major compound fisetin inhibits inflammation-related cytokines and angiogenic factor in rheumatoid arthritic fibroblast-like synovial cells and in vivo models. Int Immunopharmacol 2009; 9 (03) 268-276
- 38 Bae JS. Role of high mobility group box 1 in inflammatory disease: focus on sepsis. Arch Pharm Res 2012; 35 (09) 1511-1523
- 39 Russell JA, Walley KR. Update in sepsis 2012. Am J Respir Crit Care Med 2013; 187 (12) 1303-1307
- 40 Liu G, Wang J, Park YJ. , et al. High mobility group protein-1 inhibits phagocytosis of apoptotic neutrophils through binding to phosphatidylserine. J Immunol 2008; 181 (06) 4240-4246
- 41 Friggeri A, Yang Y, Banerjee S, Park YJ, Liu G, Abraham E. HMGB1 inhibits macrophage activity in efferocytosis through binding to the alphavbeta3-integrin. Am J Physiol Cell Physiol 2010; 299 (06) C1267-C1276
- 42 Pisetsky DS. The role of HMGB1 in efferocytosis: when the dead go unburied. Focus on “HMGB1 inhibits macrophage activity in efferocytosis through binding to the alphavbeta3-integrin”. Am J Physiol Cell Physiol 2010; 299 (06) C1253-C1255
- 43 Poon IK, Lucas CD, Rossi AG, Ravichandran KS. Apoptotic cell clearance: basic biology and therapeutic potential. Nat Rev Immunol 2014; 14 (03) 166-180
- 44 Matsuda A, Jacob A, Wu R. , et al. Milk fat globule-EGF factor VIII in sepsis and ischemia-reperfusion injury. Mol Med 2011; 17 (1-2): 126-133
- 45 Hou J, Chen Q, Zhang K. , et al. Sphingosine 1-phosphate receptor 2 signaling suppresses macrophage phagocytosis and impairs host defense against sepsis. Anesthesiology 2015; 123 (02) 409-422
- 46 Shetty S, Weston CJ, Oo YH. , et al. Common lymphatic endothelial and vascular endothelial receptor-1 mediates the transmigration of regulatory T cells across human hepatic sinusoidal endothelium. J Immunol 2011; 186 (07) 4147-4155
- 47 Salmi M, Koskinen K, Henttinen T, Elima K, Jalkanen S. CLEVER-1 mediates lymphocyte transmigration through vascular and lymphatic endothelium. Blood 2004; 104 (13) 3849-3857
- 48 Astiz ME, Rackow EC. Septic shock. Lancet 1998; 351 (9114): 1501-1505
- 49 Gordon S. The macrophage: past, present and future. Eur J Immunol 2007; 37 (Suppl. 01) S9-S17
- 50 Hanayama R, Tanaka M, Miyasaka K. , et al. Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. Science 2004; 304 (5674): 1147-1150
- 51 Hanayama R, Tanaka M, Miwa K, Shinohara A, Iwamatsu A, Nagata S. Identification of a factor that links apoptotic cells to phagocytes. Nature 2002; 417 (6885): 182-187
- 52 Cui T, Miksa M, Wu R. , et al. Milk fat globule epidermal growth factor 8 attenuates acute lung injury in mice after intestinal ischemia and reperfusion. Am J Respir Crit Care Med 2010; 181 (03) 238-246
- 53 Brissette MJ, Lepage S, Lamonde AS. , et al. MFG-E8 released by apoptotic endothelial cells triggers anti-inflammatory macrophage reprogramming. PLoS One 2012; 7 (04) e36368
- 54 Mogensen TH. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev 2009; 22 (02) 240-273
- 55 Herold S, Mayer K, Lohmeyer J. Acute lung injury: how macrophages orchestrate resolution of inflammation and tissue repair. Front Immunol 2011; 2: 65
- 56 Belaaouaj A, McCarthy R, Baumann M. , et al. Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis. Nat Med 1998; 4 (05) 615-618
- 57 Czermak BJ, Sarma V, Pierson CL. , et al. Protective effects of C5a blockade in sepsis. Nat Med 1999; 5 (07) 788-792
- 58 Underhill DM, Ozinsky A. Phagocytosis of microbes: complexity in action. Annu Rev Immunol 2002; 20: 825-852
- 59 Palani S, Elima K, Ekholm E, Jalkanen S, Salmi M. Monocyte stabilin-1 suppresses the activation of Th1 lymphocytes. J Immunol 2016; 196 (01) 115-123
- 60 Hotchkiss RS, Coopersmith CM, McDunn JE, Ferguson TA. The sepsis seesaw: tilting toward immunosuppression. Nat Med 2009; 15 (05) 496-497
- 61 Ranieri VM, Thompson BT, Barie PS. , et al; PROWESS-SHOCK Study Group. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med 2012; 366 (22) 2055-2064