Platelets support pulmonary recruitment of neutrophils in abdominal sepsis
(2009) In Critical Care Medicine 37(4). p.1389-1396- Abstract
- Objective. Recent findings Indicate that platelets not only regulate thrombosis and hemostasis but may also be involved in proinflammatory activities. Herein, we hypothesized that platelets may play a role in sepsis by activating and priming circulating neutrophils for subsequent recruitment Into the lung. Design: Prospective experimental study. Setting. University Hospital Research Unit. Subject. Male C57BL/6 mice. Interventions. Lung edema, bronchoalveolar infiltration of neutrophils, levels of myeloperoxidase, expression and function of membrane-activated complex-1 (Mac-1) on neutrophils and the CXC chemokines, macrophage inflammatory protein-2, and cytokine-induced neutrophil chemoattractant were determined after cecal ligation and... (More)
- Objective. Recent findings Indicate that platelets not only regulate thrombosis and hemostasis but may also be involved in proinflammatory activities. Herein, we hypothesized that platelets may play a role in sepsis by activating and priming circulating neutrophils for subsequent recruitment Into the lung. Design: Prospective experimental study. Setting. University Hospital Research Unit. Subject. Male C57BL/6 mice. Interventions. Lung edema, bronchoalveolar infiltration of neutrophils, levels of myeloperoxidase, expression and function of membrane-activated complex-1 (Mac-1) on neutrophils and the CXC chemokines, macrophage inflammatory protein-2, and cytokine-induced neutrophil chemoattractant were determined after cecal ligation and puncture (CLP). Mice received a platelet-depleting antibody as well as antibodies directed against P-selectin glycoprotein-ligand-1 and Mac-1 before CLP induction. Measurements and Main Results. CLP caused significant pulmonary damage characterized by neutrophil infiltration, increased levels of CXC chemokines, and edema formation in the lung. Furthermore, CLP up-regulated Mac-1 expression on neutrophils and increased the number of neutrophils binding platelets in the circulation. Interestingly, depletion of platelets reduced CLP-induced edema and neutrophil recruitment in the bronchoalveolar space by >60%. Furthermore, depletion of platelets reduced Mac-1 expression on neutrophils. On the other hand, inhibition of P-selectin glycoprotein-ligand-1 abolished CLP-induced neutrophil-platelet aggregation but had no effect on neutrophil expression of Mac-1. Conclusions: These data demonstrate that platelets play a key role in regulating infiltration of neutrophils and edema formation in the lung via upregulation of Mac-1 in abdominal sepsis. (Crit Care Med 2009; 37:1389-1396) (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1401114
- author
- Muhammad, Asad
LU
; Lavasani, Shahram
LU
; Rahman, Milladur
LU
; Zhang, Su LU ; Braun, Oscar LU ; Jeppsson, Bengt LU and Thorlacius, Henrik LU
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- lung, platelets, adhesion, neutrophils, sepsis
- in
- Critical Care Medicine
- volume
- 37
- issue
- 4
- pages
- 1389 - 1396
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- wos:000264699000030
- pmid:19242347
- scopus:67650472342
- ISSN
- 1530-0293
- DOI
- 10.1097/CCM.0b013e31819ceb71
- language
- English
- LU publication?
- yes
- id
- dced5300-a02c-4970-9a15-ee20b088b827 (old id 1401114)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/19242347?dopt=Abstract
- date added to LUP
- 2016-04-01 12:15:23
- date last changed
- 2022-04-21 04:53:17
@article{dced5300-a02c-4970-9a15-ee20b088b827, abstract = {{Objective. Recent findings Indicate that platelets not only regulate thrombosis and hemostasis but may also be involved in proinflammatory activities. Herein, we hypothesized that platelets may play a role in sepsis by activating and priming circulating neutrophils for subsequent recruitment Into the lung. Design: Prospective experimental study. Setting. University Hospital Research Unit. Subject. Male C57BL/6 mice. Interventions. Lung edema, bronchoalveolar infiltration of neutrophils, levels of myeloperoxidase, expression and function of membrane-activated complex-1 (Mac-1) on neutrophils and the CXC chemokines, macrophage inflammatory protein-2, and cytokine-induced neutrophil chemoattractant were determined after cecal ligation and puncture (CLP). Mice received a platelet-depleting antibody as well as antibodies directed against P-selectin glycoprotein-ligand-1 and Mac-1 before CLP induction. Measurements and Main Results. CLP caused significant pulmonary damage characterized by neutrophil infiltration, increased levels of CXC chemokines, and edema formation in the lung. Furthermore, CLP up-regulated Mac-1 expression on neutrophils and increased the number of neutrophils binding platelets in the circulation. Interestingly, depletion of platelets reduced CLP-induced edema and neutrophil recruitment in the bronchoalveolar space by >60%. Furthermore, depletion of platelets reduced Mac-1 expression on neutrophils. On the other hand, inhibition of P-selectin glycoprotein-ligand-1 abolished CLP-induced neutrophil-platelet aggregation but had no effect on neutrophil expression of Mac-1. Conclusions: These data demonstrate that platelets play a key role in regulating infiltration of neutrophils and edema formation in the lung via upregulation of Mac-1 in abdominal sepsis. (Crit Care Med 2009; 37:1389-1396)}}, author = {{Muhammad, Asad and Lavasani, Shahram and Rahman, Milladur and Zhang, Su and Braun, Oscar and Jeppsson, Bengt and Thorlacius, Henrik}}, issn = {{1530-0293}}, keywords = {{lung; platelets; adhesion; neutrophils; sepsis}}, language = {{eng}}, number = {{4}}, pages = {{1389--1396}}, publisher = {{Lippincott Williams & Wilkins}}, series = {{Critical Care Medicine}}, title = {{Platelets support pulmonary recruitment of neutrophils in abdominal sepsis}}, url = {{http://dx.doi.org/10.1097/CCM.0b013e31819ceb71}}, doi = {{10.1097/CCM.0b013e31819ceb71}}, volume = {{37}}, year = {{2009}}, }