Platelet-Derived CD40L (CD154) Mediates Neutrophil Upregulation of Mac-1 and Recruitment in Septic Lung Injury.
Rahman, Milladur LU
; Zhang, Su
LU
; Chew, Michelle
LU
; Ersson, Anders
LU
; Jeppsson, Bengt
LU
and Thorlacius, Henrik
LU
(2009)
In Annals of Surgery
- Abstract
- OBJECTIVE:: To define the role of CD40L in abdominal sepsis. BACKGROUND:: Platelets promote sepsis-induced pulmonary recruitment of neutrophils. However, the identity of the platelet-derived molecule regulating neutrophil infiltration is not known. The hypothesis of the present study was that platelet-derived CD40L might be responsible for platelet-mediated activation and accumulation of neutrophils in sepsis. METHODS:: Wild-type C57BL/6 mice and CD40L gene-deficient mice were exposed to cecal ligation and puncture (CLP). Lung edema, bronchoalveolar neutrophils, CD40L and macrophage inflammatory protein-2 (MIP-2) plasma levels, myeloperoxidase activity and Mac-1 expression were determined up to 24 hours after CLP induction. For platelet... (More)
- OBJECTIVE:: To define the role of CD40L in abdominal sepsis. BACKGROUND:: Platelets promote sepsis-induced pulmonary recruitment of neutrophils. However, the identity of the platelet-derived molecule regulating neutrophil infiltration is not known. The hypothesis of the present study was that platelet-derived CD40L might be responsible for platelet-mediated activation and accumulation of neutrophils in sepsis. METHODS:: Wild-type C57BL/6 mice and CD40L gene-deficient mice were exposed to cecal ligation and puncture (CLP). Lung edema, bronchoalveolar neutrophils, CD40L and macrophage inflammatory protein-2 (MIP-2) plasma levels, myeloperoxidase activity and Mac-1 expression were determined up to 24 hours after CLP induction. For platelet depletion was an anti-GP1balpha antibody administered before CLP. RESULTS:: Plasma levels of soluble CD40L increased and surface expression of CD40L on platelets decreased in CLP mice. Platelet depletion reduced CLP-induced CD40L levels by 90%. CLP-provoked Mac-1 expression on neutrophils was abolished in CD40L-deficient mice. Interestingly, CLP-induced edema and myeloperoxidase activity in the lung as well as neutrophil infiltration in the broncoalveolar space were markedly reduced in mice lacking CD40L. In vitro experiments showed that CD40L was not capable of directly increasing Mac-1 levels on neutrophils. Instead, CLP-induced plasma levels of MIP-2 were significantly reduced in CD40L-deficient mice and inhibition of the MIP-2 receptor (CXCR2) decreased Mac-1 expression on neutrophils in septic animals. CONCLUSIONS:: CD40L derived from platelets is a potent activator of neutrophils and mediates sepsis-induced neutrophil recruitment and lung edema. The neutrophil activating mechanism of CD40L is indirect and mediated via MIP-2 formation and CXCR2 signaling. Targeting CD40L may be an effective approach to limit pulmonary damage in abdominal sepsis. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1500627
- author
- Rahman, Milladur
LU
; Zhang, Su
LU
; Chew, Michelle
LU
; Ersson, Anders
LU
; Jeppsson, Bengt
LU
and Thorlacius, Henrik
LU
- organization
- publishing date
- 2009-10-02
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Annals of Surgery
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- pmid:19806052
- scopus:70449393352
- pmid:19806052
- ISSN
- 1528-1140
- DOI
- 10.1097/SLA.0b013e3181bd95b7
- language
- English
- LU publication?
- yes
- id
- 73c26db4-87f3-42f0-9e98-80b135fd34e2 (old id 1500627)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/19806052?dopt=Abstract
- date added to LUP
- 2016-04-04 08:04:56
- date last changed
- 2022-01-29 02:59:53
@article{73c26db4-87f3-42f0-9e98-80b135fd34e2,
abstract = {{OBJECTIVE:: To define the role of CD40L in abdominal sepsis. BACKGROUND:: Platelets promote sepsis-induced pulmonary recruitment of neutrophils. However, the identity of the platelet-derived molecule regulating neutrophil infiltration is not known. The hypothesis of the present study was that platelet-derived CD40L might be responsible for platelet-mediated activation and accumulation of neutrophils in sepsis. METHODS:: Wild-type C57BL/6 mice and CD40L gene-deficient mice were exposed to cecal ligation and puncture (CLP). Lung edema, bronchoalveolar neutrophils, CD40L and macrophage inflammatory protein-2 (MIP-2) plasma levels, myeloperoxidase activity and Mac-1 expression were determined up to 24 hours after CLP induction. For platelet depletion was an anti-GP1balpha antibody administered before CLP. RESULTS:: Plasma levels of soluble CD40L increased and surface expression of CD40L on platelets decreased in CLP mice. Platelet depletion reduced CLP-induced CD40L levels by 90%. CLP-provoked Mac-1 expression on neutrophils was abolished in CD40L-deficient mice. Interestingly, CLP-induced edema and myeloperoxidase activity in the lung as well as neutrophil infiltration in the broncoalveolar space were markedly reduced in mice lacking CD40L. In vitro experiments showed that CD40L was not capable of directly increasing Mac-1 levels on neutrophils. Instead, CLP-induced plasma levels of MIP-2 were significantly reduced in CD40L-deficient mice and inhibition of the MIP-2 receptor (CXCR2) decreased Mac-1 expression on neutrophils in septic animals. CONCLUSIONS:: CD40L derived from platelets is a potent activator of neutrophils and mediates sepsis-induced neutrophil recruitment and lung edema. The neutrophil activating mechanism of CD40L is indirect and mediated via MIP-2 formation and CXCR2 signaling. Targeting CD40L may be an effective approach to limit pulmonary damage in abdominal sepsis.}},
author = {{Rahman, Milladur and Zhang, Su and Chew, Michelle and Ersson, Anders and Jeppsson, Bengt and Thorlacius, Henrik}},
issn = {{1528-1140}},
language = {{eng}},
month = {{10}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{Annals of Surgery}},
title = {{Platelet-Derived CD40L (CD154) Mediates Neutrophil Upregulation of Mac-1 and Recruitment in Septic Lung Injury.}},
url = {{http://dx.doi.org/10.1097/SLA.0b013e3181bd95b7}},
doi = {{10.1097/SLA.0b013e3181bd95b7}},
year = {{2009}},
}