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Direct in vivo observations of P-selectin glycoprotein ligand-1-mediated leukocyte-endothelial cell interactions in the pulmonary microvasculature in abdominal sepsis in mice.

Roller, Jonas LU ; Wang, Yusheng LU ; Rahman, Milladur LU ; Schramm, R ; Laschke, M W ; Menger, M D ; Jeppsson, Bengt LU and Thorlacius, Henrik LU (2013) In Inflammation Research 62(3). p.275-282
Abstract
OBJECTIVE: P-selectin glycoprotein ligand-1 (PSGL-1) has been shown to play a significant role in septic lung injury. However, the detailed role of PSGL-1 in the pulmonary leukocyte recruitment remains elusive. We have developed a method based on intravital fluorescence microscopy of the lung microcirculation to examine the role of PSGL-1 in the extravasation process of leukocytes in septic lung damage. METHODS: Male C57BL/6 mice were treated with a control antibody or an anti-PSGL-1 antibody prior to cecal ligation and puncture (CLP). Leukocyte-endothelium interactions and microvascular hemodynamics were studied in pulmonary arterioles, capillaries and venules 4 h after CLP. RESULTS: Immunoneutralization of PSGL-1 decreased CLP-induced... (More)
OBJECTIVE: P-selectin glycoprotein ligand-1 (PSGL-1) has been shown to play a significant role in septic lung injury. However, the detailed role of PSGL-1 in the pulmonary leukocyte recruitment remains elusive. We have developed a method based on intravital fluorescence microscopy of the lung microcirculation to examine the role of PSGL-1 in the extravasation process of leukocytes in septic lung damage. METHODS: Male C57BL/6 mice were treated with a control antibody or an anti-PSGL-1 antibody prior to cecal ligation and puncture (CLP). Leukocyte-endothelium interactions and microvascular hemodynamics were studied in pulmonary arterioles, capillaries and venules 4 h after CLP. RESULTS: Immunoneutralization of PSGL-1 decreased CLP-induced leukocyte rolling in pulmonary arterioles and venules significantly. Inhibition of PSGL-1 had no effect on leukocyte adhesion in venules, whereas the number of adherent leukocytes in lung arterioles and the number of trapped leukocytes in capillaries were markedly decreased. Moreover, immunoneutralization of PSGL-1 improved microvascular perfusion in the lung of septic animals. CONCLUSIONS: Taken together, these results document that PSGL-1 mediates leukocyte rolling in arterioles and venules. However, inhibition of PSGL-1 only decreases leukocyte adhesion in arterioles, suggesting that leukocyte rolling is not a prerequisite for pulmonary venular adhesion of leukocytes in sepsis. In addition, our data show that capillary trapping of leukocytes is dependent on PSGL-1 function. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Inflammation Research
volume
62
issue
3
pages
275 - 282
publisher
Birkhaüser
external identifiers
  • wos:000314776000003
  • pmid:23178793
  • scopus:84877155448
  • pmid:23178793
ISSN
1420-908X
DOI
10.1007/s00011-012-0575-y
language
English
LU publication?
yes
id
048e3310-b72d-43cd-aade-0155d3cb551c (old id 3218517)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23178793?dopt=Abstract
date added to LUP
2016-04-01 10:01:06
date last changed
2020-01-05 04:08:37
@article{048e3310-b72d-43cd-aade-0155d3cb551c,
  abstract     = {OBJECTIVE: P-selectin glycoprotein ligand-1 (PSGL-1) has been shown to play a significant role in septic lung injury. However, the detailed role of PSGL-1 in the pulmonary leukocyte recruitment remains elusive. We have developed a method based on intravital fluorescence microscopy of the lung microcirculation to examine the role of PSGL-1 in the extravasation process of leukocytes in septic lung damage. METHODS: Male C57BL/6 mice were treated with a control antibody or an anti-PSGL-1 antibody prior to cecal ligation and puncture (CLP). Leukocyte-endothelium interactions and microvascular hemodynamics were studied in pulmonary arterioles, capillaries and venules 4 h after CLP. RESULTS: Immunoneutralization of PSGL-1 decreased CLP-induced leukocyte rolling in pulmonary arterioles and venules significantly. Inhibition of PSGL-1 had no effect on leukocyte adhesion in venules, whereas the number of adherent leukocytes in lung arterioles and the number of trapped leukocytes in capillaries were markedly decreased. Moreover, immunoneutralization of PSGL-1 improved microvascular perfusion in the lung of septic animals. CONCLUSIONS: Taken together, these results document that PSGL-1 mediates leukocyte rolling in arterioles and venules. However, inhibition of PSGL-1 only decreases leukocyte adhesion in arterioles, suggesting that leukocyte rolling is not a prerequisite for pulmonary venular adhesion of leukocytes in sepsis. In addition, our data show that capillary trapping of leukocytes is dependent on PSGL-1 function.},
  author       = {Roller, Jonas and Wang, Yusheng and Rahman, Milladur and Schramm, R and Laschke, M W and Menger, M D and Jeppsson, Bengt and Thorlacius, Henrik},
  issn         = {1420-908X},
  language     = {eng},
  number       = {3},
  pages        = {275--282},
  publisher    = {Birkhaüser},
  series       = {Inflammation Research},
  title        = {Direct in vivo observations of P-selectin glycoprotein ligand-1-mediated leukocyte-endothelial cell interactions in the pulmonary microvasculature in abdominal sepsis in mice.},
  url          = {https://lup.lub.lu.se/search/ws/files/1482261/3737264.pdf},
  doi          = {10.1007/s00011-012-0575-y},
  volume       = {62},
  year         = {2013},
}