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Hemorrhagic shock primes for increased expression of cytokine‐induced neutrophil chemoattractant in the lung: role in pulmonary inflammation following lipopolysaccharide
Open accessAbstract
Recent studies have suggested that hemorrhagic shock followed by resuscitation renders patients more susceptible to lung injury by priming for an exaggerated response to a second stimulus, the so-called "two-hit" hypothesis. We investigated the role of C-X-C chemokines in mediating the augmented lung inflammation in response to LPS following resuscitated shock. In a rodent model, animals exposed to antecedent shock exhibited enhanced lung neutrophil sequestration and transpulmonary albumin flux in response to intratracheal LPS. This effect correlated with an exaggerated expression of cytokine-induced neutrophil chemoattractant (CINC) protein and mRNA, but not macrophage-inflammatory protein 2. Strategies designed to inhibit CINC, both anti-CINC Ab and supplementation with the antioxidant N-acetyl-cysteine, prevented the enhanced neutrophil sequestration, suggesting that CINC played a central role in the enhanced leukocyte accumulation following shock plus LPS treatment. Shock alone increased lung nuclear factor-kappaB expression and augmented the response to LPS. Prevention of this effect by N-acetylcysteine supplementation of the resuscitation fluid implicates a role for oxidant stress in the priming for lung inflammation following shock. Finally, alveolar macrophages recovered from shock-resuscitated animals released more CINC protein in vitro in response to LPS than macrophages from sham animals. Considered together, these findings show that augmented release of CINC, in part from primed alveolar macrophages, contributes significantly to the enhanced lung leukosequestration and transpulmonary albumin flux in response to LPS following resuscitated shock.
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“It has long been known that patients in intensive care suffering from shock, infection, or trauma react inadequately to a renewed challenge like surgery. This has also been called the phenomenon of the second hit.126, 127, 128, 129, 130, 131”
From Hypoalbuminemia: Pathogenesis and Clinical Significance (2019) · cites this paper as [127]
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Metadata
- Authors
- Fan, J., Marshall, J. C., Jimenez, M., Shek, P. N., Zagorski, J., & Rotstein, O. D.
- Affiliations
- University of Toronto (CA)
- Defense and Civil Institute of Environmental Medicine , Toronto, Ontario ,
- National Institutes of Health (US)
- Corresponding author
- Fan, Jie
- Jimenez, Maria
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1998-07-01
- Volume
- 161
- Issue
- 1
- Pages
- 440-447
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1902960727
- Cited by
- 193
- References
- 41
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 4 · 2018: 5 · 2017: 1 · 2016: 2 · 2015: 8 · 2014: 7 · 2013: 7 · 2012: 12
- FWCI
- 10.40
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Repositorio Institucional (Pontificia Universidad Javeriana) (submittedVersion, cc-by-nc)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Trauma, Hemostasis, Coagulopathy, Resuscitation
- Keywords
- hemorrhagic shock, resuscitation, two-hit hypothesis, CXC chemokines, cytokine-induced neutrophil chemoattractant, lipopolysaccharide, lung inflammation, neutrophil sequestration, alveolar macrophages, oxidative stress, N-acetylcysteine, NF-κB, neutrophil recruitment
- MeSH terms
- Acetylcysteine, Albumins, Animals, Biological Transport, Chemotactic Factors, Growth Substances, Immune Sera, Lipopolysaccharides, Lung, Male, Neutrophils, Shock, Hemorrhagic, Cytokines, NF-kappa B, Macrophages, Alveolar, Oxidants, Rats, Sprague-Dawley, Chemokines, CXC, Intercellular Signaling Peptides and Proteins, Rats, Chemokine CXCL2
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