The role and mechanism of P-selectin glycoprotein ligand-1 in hydrochloric acid-induced lung injury in mice_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

LIU Zeyu ¹ , JIANG Baozhen ¹ , YANG Zhiwei ² ,  LIU Xing ² ,  ZHANG Zhihong ¹

1. Department of Geriatric Pulmology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230000, P.R.China;
2. Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Beijing 100021, P.R.China;

Corresponding author：

LIU Xing, Email: xingliu1976@163.com; ZHANG Zhihong, Email: zhangzhihope@hotmail.com

Keywords：

P-selectin glycoprotein ligand-1; Acute lung injury; Nuclear factor-κB

DOI：

10.7507/1671-6205.201701005

Video：

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ObjectiveTo investigate the role and mechanism of P-selectin glycoprotein ligand-1 (PSGL-1) in hydrochloric acid-induced acute lung injury (ALI) in mice.MethodsWild-type mice (WT) and PSGL-1 knockout mice (PSGL-1 -/-) were randomly subjected to normal saline (NS) or hydrochloric acid (HCl) challenged group. The mice were intratracheally instilled with NS or HCl (1 μl/g weight) into the left lung with a catheter. After 2 hours, respiratory function index enhanced pause (Penh), PaO₂ and PaO₂ were analyzed. The wet to dry weight ratio (W/D) of the left lung and total protein concentration in bronchoalveolar lavage fluid (BALF) were measured. The number of leukocytes in BALF was counted too. Targeted lung tissue was processed for further HE or immunohistochemistry staining. Meanwhile, the expressions of interleukin-6 (IL-6), IL-1β, nuclear factor-κB (NF-κB), IκBa and p-IκBa in lung tissue were measured.ResultsThe Penh (4.77±1.22 vs. 5.80±0.84) and PaCO₂ [(63.7±3.9) mm Hg vs. (74.4±7.4) mm Hg] in the PSGL-1 knockout mice were significantly lower than those in the WT mice after HCl stimulation (P<0.05), while the PaO₂ was higher than that in the WT mice [(81.0±7.1) mm Hg vs. (62.0±8.9) mm Hg, P<0.05)]. The lung W/D ratio (4.86±0.15 vs. 5.22±0.20), protein concentration [(3.71±0.64) μg/μl vs. (4.74±0.98) μg/μl] and total leukocyte count [(13.00±2.18) ×10⁷/L vs. (49.42±3.35) ×10⁷/L] in BALF were significantly lower in the PSGL-1 knockout mice challenged with HCl than those in the WT mice (P<0.05). Besides, the protein expressions of IL-6, IL-1β, p65 and p-IκBa in the PSGL-1 knockout mice were lower than those in the WT mice after HCl instillation, while the IκBa expression was higher than that in the WT mice (P<0.05). More numbers of neutrophils and macrophages were found in the lung of the WT mice than the PSGL-1 knockout mice challenged with HCl. However, the differences of above values between the WT mice and the PSGL-1 knockout mice instilled with NS were not found, all of which were significantly lower than the correspongding HCl group except for IκBa (P<0.05).ConclusionPSGL-1 may play important roles in the development of HCl-induced ALI via the NF-κB signaling pathway and inflammation.

Citation： LIU Zeyu, JIANG Baozhen, YANG Zhiwei, LIU Xing, ZHANG Zhihong. The role and mechanism of P-selectin glycoprotein ligand-1 in hydrochloric acid-induced lung injury in mice. Chinese Journal of Respiratory and Critical Care Medicine, 2017, 16(4): 394-400. doi: 10.7507/1671-6205.201701005 Copy

1.	Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA, 2012, 307(23): 2526-2533.
2.	Zhang Y, Zhao Z, Guan L, et al. N-acetyl-heparin attenuates acute lung injury caused by acid aspiration mainly by antagonizing histones in mice. PLoS One, 2014, 9(5): e97074.
3.	De Backer D, Orbegozo CD, Donadello K, et al. Pathophysiology of microcirculatory dysfunction and the pathogenesis of septic shock. Virulence, 2014, 5(1): 73-79.
4.	Gill SE, Rohan M, Mehta S. Role of pulmonary microvascular endothelial cell apoptosis in murine sepsis-induced lung injury in vivo. Respir Res, 2015, 16(1): 109.
5.	Wang L, Taneja R, Razavi HM, et al. Specific role of neutrophil inducible nitric oxide synthase in murine sepsis-induced lung injury in vivo. Shock, 2012, 37(5): 539-547.
6.	Mcever RP, Beckstead J H, Moore K L, et al. GMP-140, a platelet alpha-granule membrane protein, is also synthesized by vascular endothelial cells and is localized in Weibel-Palade bodies. J Clin Invest, 1989, 84(1): 92-99.
7.	Zhou T, Li X, Wu P, et al. Effect of anti-P-selectin monoclonal antibody on renal ischemia/reperfusion injury in rats. Chin Med J (Engl), 2000, 113(9): 790-793.
8.	Mcever RP, Cummings RD. Perspectives series: cell adhesion in vascular biology. Role of PSGL-1 binding to selectins in leukocyte recruitment. J Clin Invest, 1997, 100(3): 485-491.
9.	Mehta P, Cummings RD, Mcever RP. Affinity and kinetic analysis of P-selectin binding to P-selectin glycoprotein ligand-1. J Biol Chem, 1998, 273(49): 32506-32513.
10.	Raghavendran K, Nemzek J, Napolitano LM, et al. Aspiration-induced lung injury. Crit Care Med, 2011, 39(4): 818-826.
11.	Konstantopoulos K, Mcintire LV. Effects of fluid dynamic forces on vascular cell adhesion. J Clin Invest, 1997, 100(11 Suppl): S19-S23.
12.	Springer TA. Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Annu Rev Physiol, 1995, 57: 827-872.
13.	Zimmerman GA, Mcintyre TM, Prescott SM. Adhesion and signaling in vascular cell-cell interactions. J Clin Invest, 1997, 100(11 Suppl): S3-S5.
14.	Zarbock A, Abram C L, Hundt M, et al. PSGL-1 engagement by E-selectin signals through Src kinase Fgr and ITAM adapters DAP12 and FcR gamma to induce slow leukocyte rolling. J Exp Med, 2008, 205(10): 2339-2347.
15.	Borges E, Eytner R, Moll T, et al. The P-selectin glycoprotein ligand-1 is important for recruitment of neutrophils into inflamed mouse peritoneum. Blood, 1997, 90(5): 1934-1942.
16.	Yang J, Hirata T, Croce K, et al. Targeted gene disruption demonstrates that P-selectin glycoprotein ligand 1 (PSGL-1) is required for P-selectin-mediated but not E-selectin-mediated neutrophil rolling and migration. J Exp Med, 1999, 190(12): 1769-1782.
17.	Pasparakis M. Regulation of tissue homeostasis by NF-kappaB signalling: implications for inflammatory diseases. Nat Rev Immunol, 2009, 9(11): 778-788.
18.	Galani V, Tatsaki E, Bai M, et al. The role of apoptosis in the pathophysiology of acute respiratory distress syndrome (ARDS): an up-to-date cell-specific review. Pathol Res Pract, 2010, 206(3): 145-150.
19.	Lopez B, Maisonet TM, Londhe VA. Alveolar NF-kappaB signaling regulates endotoxin-induced lung inflammation. Exp Lung Res, 2015, 41(2): 103-114.
20.	Baker RG, Hayden MS, Ghosh S. NF-kappaB, inflammation, and metabolic disease. Cell Metab, 2011, 13(1): 11-22.
21.	Lawrence T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol, 2009, 1(6): a1651.
22.	Matthay MA, Zimmerman GA, Esmon C, et al. Future research directions in acute lung injury: summary of a National Heart, Lung, and Blood Institute working group. Am J Respir Crit Care Med, 2003, 167(7): 1027-1035.
23.	Ptasinska A, Assi SA, Mannari D, et al. Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding. Leukemia, 2012, 26(8): 1829-1841.

1. Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA, 2012, 307(23): 2526-2533.
2. Zhang Y, Zhao Z, Guan L, et al. N-acetyl-heparin attenuates acute lung injury caused by acid aspiration mainly by antagonizing histones in mice. PLoS One, 2014, 9(5): e97074.
3. De Backer D, Orbegozo CD, Donadello K, et al. Pathophysiology of microcirculatory dysfunction and the pathogenesis of septic shock. Virulence, 2014, 5(1): 73-79.
4. Gill SE, Rohan M, Mehta S. Role of pulmonary microvascular endothelial cell apoptosis in murine sepsis-induced lung injury in vivo. Respir Res, 2015, 16(1): 109.
5. Wang L, Taneja R, Razavi HM, et al. Specific role of neutrophil inducible nitric oxide synthase in murine sepsis-induced lung injury in vivo. Shock, 2012, 37(5): 539-547.
6. Mcever RP, Beckstead J H, Moore K L, et al. GMP-140, a platelet alpha-granule membrane protein, is also synthesized by vascular endothelial cells and is localized in Weibel-Palade bodies. J Clin Invest, 1989, 84(1): 92-99.
7. Zhou T, Li X, Wu P, et al. Effect of anti-P-selectin monoclonal antibody on renal ischemia/reperfusion injury in rats. Chin Med J (Engl), 2000, 113(9): 790-793.
8. Mcever RP, Cummings RD. Perspectives series: cell adhesion in vascular biology. Role of PSGL-1 binding to selectins in leukocyte recruitment. J Clin Invest, 1997, 100(3): 485-491.
9. Mehta P, Cummings RD, Mcever RP. Affinity and kinetic analysis of P-selectin binding to P-selectin glycoprotein ligand-1. J Biol Chem, 1998, 273(49): 32506-32513.
10. Raghavendran K, Nemzek J, Napolitano LM, et al. Aspiration-induced lung injury. Crit Care Med, 2011, 39(4): 818-826.
11. Konstantopoulos K, Mcintire LV. Effects of fluid dynamic forces on vascular cell adhesion. J Clin Invest, 1997, 100(11 Suppl): S19-S23.
12. Springer TA. Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Annu Rev Physiol, 1995, 57: 827-872.
13. Zimmerman GA, Mcintyre TM, Prescott SM. Adhesion and signaling in vascular cell-cell interactions. J Clin Invest, 1997, 100(11 Suppl): S3-S5.
14. Zarbock A, Abram C L, Hundt M, et al. PSGL-1 engagement by E-selectin signals through Src kinase Fgr and ITAM adapters DAP12 and FcR gamma to induce slow leukocyte rolling. J Exp Med, 2008, 205(10): 2339-2347.
15. Borges E, Eytner R, Moll T, et al. The P-selectin glycoprotein ligand-1 is important for recruitment of neutrophils into inflamed mouse peritoneum. Blood, 1997, 90(5): 1934-1942.
16. Yang J, Hirata T, Croce K, et al. Targeted gene disruption demonstrates that P-selectin glycoprotein ligand 1 (PSGL-1) is required for P-selectin-mediated but not E-selectin-mediated neutrophil rolling and migration. J Exp Med, 1999, 190(12): 1769-1782.
17. Pasparakis M. Regulation of tissue homeostasis by NF-kappaB signalling: implications for inflammatory diseases. Nat Rev Immunol, 2009, 9(11): 778-788.
18. Galani V, Tatsaki E, Bai M, et al. The role of apoptosis in the pathophysiology of acute respiratory distress syndrome (ARDS): an up-to-date cell-specific review. Pathol Res Pract, 2010, 206(3): 145-150.
19. Lopez B, Maisonet TM, Londhe VA. Alveolar NF-kappaB signaling regulates endotoxin-induced lung inflammation. Exp Lung Res, 2015, 41(2): 103-114.
20. Baker RG, Hayden MS, Ghosh S. NF-kappaB, inflammation, and metabolic disease. Cell Metab, 2011, 13(1): 11-22.
21. Lawrence T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol, 2009, 1(6): a1651.
22. Matthay MA, Zimmerman GA, Esmon C, et al. Future research directions in acute lung injury: summary of a National Heart, Lung, and Blood Institute working group. Am J Respir Crit Care Med, 2003, 167(7): 1027-1035.
23. Ptasinska A, Assi SA, Mannari D, et al. Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding. Leukemia, 2012, 26(8): 1829-1841.

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The role and mechanism of P-selectin glycoprotein ligand-1 in hydrochloric acid-induced lung injury in mice

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