Sepsis-induced leukocyte adhesion in the pulmonary microvasculature in vivo is mediated by CD11a and CD11b

Wang, Yongzhi; Roller, Jonas; Menger, Michael D.; Thorlacius, Henrik

doi:10.1016/j.ejphar.2013.01.024

Cited by 28 publications

(25 citation statements)

References 37 publications

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“…Although specific therapies directed at reducing adhesion of leukocytes such as antibodies raised against adhesion molecules like CD11a have been shown to be effective in sepsis-induced lung injury (69), no clinical therapies are available for limiting adhesion of leukocytes to the endothelium. Of course, protecting the ECL in other ways, perhaps through NO donors, could result, indirectly, in modulating leukocyte adhesion.…”

Section: Resultsmentioning

confidence: 99%

The Endothelium in Sepsis

İnce

Mayeux

Nguyen

et al. 2016

Shock

524

456

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Sepsis affects practically all aspects of endothelial cell (EC) function and is thought to be the key factor in the progression from sepsis to organ failure. Endothelial functions affected by sepsis include vasoregulation, barrier function, inflammation, and hemostasis. These are among other mechanisms often mediated by glycocalyx shedding, such as abnormal nitric oxide metabolism, up-regulation of reactive oxygen species generation due to down-regulation of endothelial-associated antioxidant defenses, transcellular communication, proteases, exposure of adhesion molecules, and activation of tissue factor. This review covers current insight in EC-associated hemostatic responses to sepsis and the EC response to inflammation. The endothelial cell lining is highly heterogeneous between different organ systems and consequently also in its response to sepsis. In this context, we discuss the response of the endothelial cell lining to sepsis in the kidney, liver, and lung. Finally, we discuss evidence as to whether the EC response to sepsis is adaptive or maladaptive. This study is a result of an Acute Dialysis Quality Initiative XIV Sepsis Workgroup meeting held in Bogota, Columbia, between October 12 and 15, 2014.

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Section: Resultsmentioning

confidence: 99%

The Endothelium in Sepsis

İnce

Mayeux

Nguyen

et al. 2016

Shock

524

456

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“…47,48 Indeed, during sepsis the integrins cd11a and cd11b are involved in leukocyte adhesion to the pulmonary vascular wall. 49 We showed here that CX3CR1 is a major determinant of this phenomenon and that CX3CR1 deficiency reduces the adhesive properties of Ly6C high monocytes. The result that CX3CR1 play a protective role during sepsis is consistent with previous work 24,46 showing that the administration of CX3CL1 can improve inflammatory response during sepsis and even reduce mortality.…”

Section: Discussionmentioning

confidence: 98%

Ly6Chigh Monocytes Protect against Kidney Damage during Sepsis via a CX3CR1-Dependent Adhesion Mechanism

Chousterman

Boissonnas

Poupel

et al. 2016

Journal of the American Society of Nephrology

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Monocytes have a crucial role in both proinflammatory and anti-inflammatory phenomena occurring during sepsis. Monocyte recruitment and activation are orchestrated by the chemokine receptors CX3CR1 and CCR2 and their cognate ligands. However, little is known about the roles of these cells and chemokines during the acute phase of inflammation in sepsis. Using intravital microscopy in a murine model of polymicrobial sepsis, we showed that inflammatory Ly6C high monocytes infiltrated kidneys, exhibited altered motility, and adhered strongly to the renal vascular wall in a chemokine receptor CX3CR1-dependent manner. Adoptive transfer of Cx3cr1-proficient monocyte-enriched bone marrow cells into septic Cx3cr1-depleted mice prevented kidney damage and promoted mouse survival. Modulation of CX3CR1 activation in septic mice controlled monocyte adhesion, regulated proinflammatory and anti-inflammatory cytokine expression, and was associated with the extent of kidney lesions such that the number of lesions decreased when CX3CR1 activity increased. Consistent with these results, the pro-adhesive I249 CX3CR1 allele in humans was associated with a lower incidence of AKI in patients with sepsis. These data show that inflammatory monocytes have a protective effect during sepsis via a CX3CR1-dependent adhesion mechanism. This receptor might be a new therapeutic target for kidney injury during sepsis.

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“…Together, these findings suggest that NETs are a potent inducer of systemic inflammation in abdominal sepsis. It is well established that neutrophil infiltration is a ratelimiting step in septic lung injury (23,47,55). It was therefore of great interest to study the effect of NET depletion on neutrophil infiltration in septic lung damage in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…In this context, it is important to note that DNAse treatment exerted no direct effect on neutrophil functions, such as CXCL2-induced Mac-1 upregulation and chemotaxis. Pulmonary recruitment of leukocytes is a multistep process, including initial sequestration in microvessels and firm adhesion on the endothelium, followed by transendothelial and transepithelial migration (47,55,56). Trafficking of leukocytes in inflamed tissues is coordinated by secreted chemokines (40,51).…”

Section: Discussionmentioning

confidence: 99%

Proinflammatory role of neutrophil extracellular traps in abdominal sepsis

Luo

Zhang

Wang

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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106

101

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Excessive neutrophil activation is a major component in septic lung injury. Neutrophil-derived DNA may form extracellular traps in response to bacterial invasions. The aim of the present study was to investigate the potential role of neutrophil extracellular traps (NETs) in septic lung injury. Male C57BL/6 mice were treated with recombinant human (rh)DNAse (5 mg/kg) after cecal ligation and puncture (CLP). Extracellular DNA was stained by Sytox green, and NET formation was quantified by confocal microscopy and cell-free DNA in plasma, peritoneal cavity, and lung. Blood, peritoneal fluid, and lung tissue were harvested for analysis of neutrophil infiltration, NET levels, tissue injury, as well as CXC chemokine and cytokine formation. We observed that CLP caused increased formation of NETs in plasma, peritoneal cavity, and lung. Administration of rhDNAse not only eliminated NET formation in plasma, peritoneal cavity, and bronchoalveolar space but also reduced lung edema and tissue damage 24 h after CLP induction. Moreover, treatment with rhDNAse decreased CLP-induced formation of CXC chemokines, IL-6, and high-mobility group box 1 (HMGB1) in plasma, as well as CXC chemokines and IL-6 in the lung. In vitro, we found that neutrophil-derived NETs had the capacity to stimulate secretion of CXCL2, TNF-α, and HMGB1 from alveolar macrophages. Taken together, our findings show that NETs regulate pulmonary infiltration of neutrophils and tissue injury via formation of proinflammatory compounds in abdominal sepsis. Thus we conclude that NETs exert a proinflammatory role in septic lung injury.

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Sepsis-induced leukocyte adhesion in the pulmonary microvasculature in vivo is mediated by CD11a and CD11b

Cited by 28 publications

References 37 publications

The Endothelium in Sepsis

The Endothelium in Sepsis

Ly6Chigh Monocytes Protect against Kidney Damage during Sepsis via a CX3CR1-Dependent Adhesion Mechanism

Proinflammatory role of neutrophil extracellular traps in abdominal sepsis

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