Regulation of Neutrophil Activation in Acute Lung Injury

Downey, Gregory P.; Dong, Qin; Kruger, Joshua M.; Dedhar, Shoukat; Cherapanov, Vera

doi:10.1016/s0012-3692(15)30668-1

Cited by 96 publications

(45 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…One possible explanation is that activation of the CD18-independent pathways is a delayed event, whereas the initial PMN sequestration depends more on CD18 integrins. As onset of the increase in endothelial permeability following activation of PMN adherent to endothelial cells is rapid (40,41), it is likely that the initial CD18 dependence of PMN sequestration would be a critical determinant of increased microvessel permeability. Another possibility is that the initial activation of PMN CD18 integrins results in the respiratory burst and release of oxidants involved in mediating lung microvascular injury (6,7).…”

Section: Discussionmentioning

confidence: 99%

Differential Role of CD18 Integrins in Mediating Lung Neutrophil Sequestration and Increased Microvascular Permeability Induced byEscherichia coliin Mice

Gao

Sekosan

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

The in vivo contributions of CD18 integrin-dependent and -independent mechanisms in mediating the increases in lung neutrophil (polymorphonuclear leukocyte; PMN) sequestration and microvascular permeability are not well understood. We determined the time course of these responses to Gram-negative sepsis in the mouse lung and addressed the specific contributions of CD18 integrins and ICAM-1. PMN sequestration in the lung was assessed by morphometric analysis, and transalveolar PMN migration was assessed by bronchoalveolar lavage. Lung tissue PMN number increased by 6-fold within 1 h after i.p. Escherichia coli challenge; this value peaked at 3 h (7-fold above control) and decreased at 12 h (3.5-fold above control). PMN migration into the airspace was delayed; the value peaked at 6 h and remained elevated up to 12 h. Saturating concentrations of anti-CD18 and anti-ICAM-1 mAbs reduced lung tissue PMN sequestration and migration; however, peak responses at 3 and 6 h were inhibited by 40%, indicating that only a small component of PMN sequestration and migration was CD18 dependent at these times. In contrast to the time-dependent decreased role of CD18 integrins in mediating PMN sequestration and migration, CD18 and ICAM-1 blockade prevented the increase in lung microvascular permeability and edema formation at all times after E. coli challenge. Thus, Gram-negative sepsis engages CD18/ICAM-1-independent mechanisms capable of the time-dependent amplification of lung PMN sequestration and migration. The increased pulmonary microvascular permeability induced by E. coli is solely the result of engagement of CD18 integrins even when PMN accumulation and migration responses are significantly CD18 independent.

show abstract

Section: Discussionmentioning

confidence: 99%

Differential Role of CD18 Integrins in Mediating Lung Neutrophil Sequestration and Increased Microvascular Permeability Induced byEscherichia coliin Mice

Gao

Sekosan

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…SIRS impairs the function of host organs by an uncontrolled self-destructive immune response that results in severe tissue damage [1]. Inflammatory lung tissue damage is a major cause of post-traumatic morbidity and mortality of intensive care patients.…”

Section: Introductionmentioning

confidence: 99%

“…Activated neutrophils play a central role in the damage of lung tissue in sepsis [1,2,16]. However, the mechanisms that control the lethal actions of neutrophils and diminish lung tissue damage in individuals who recover from sepsis are unknown.…”

Section: Introductionmentioning

confidence: 99%

Surface expression of HSP72 by LPS‐stimulated neutrophils facilitates γδT cell‐mediated killing

Hirsh¹,

Hashiguchi²,

Chen³

et al. 2006

Eur J Immunol

View full text Add to dashboard Cite

During inflammation and sepsis, accumulation of activated neutrophils causes lung tissue damage and organ failure. Effective clearance of neutrophils reduces the risk of organ failure; however, its mechanisms are poorly understood. Because lungs are rich in cdT cells, we investigated the physiological role of these cells in the protection of lung tissue from infiltrating neutrophils. In a mouse model of sepsis, we found that the lungs of survivors contained significantly higher numbers of cdT cells than those of mice that died from sepsis. The number of cdT cells correlated inversely with the number of neutrophils in the lungs and with the degree of lung tissue damage. LPS rapidly elicited the expression of heat shock protein (HSP) 72 on the surface of human neutrophils. Inhibitors of transcription, protein synthesis, and intracellular protein transport blocked HSP72 expression, indicating that de novo synthesis is required. cdT cells targeted and rapidly killed LPS-treated neutrophils through direct cell-to-cell contact. Pre-treatment with neutralizing antibodies to HSP72 diminished neutrophil killing. Our data indicate that HSP72 expression on the cell surface predisposes inflamed neutrophils to killing by cdT cells. This intercellular exchange may allow cdT cells to resolve inflammation and limit host tissue damage during sepsis.

show abstract

“…Само по себе примирование нейтрофилов не вы-зывает повреждения легких, но нарушение их жестко-сти (деформабельности) и закупорка микрососудов может быть одним из патогенетических механизмов острого воспале ния легких на фоне снижения перфу-зионного давления [12]. Согласно двухступенчатой модели активации нейтрофилов, примированные ней-трофилы должны получить второй стимул, чтобы они могли проявить цитотоксичность и вызвать поврежде-ние легких [9,13].…”

unclassified

Neutrophils and Systemic Inflammatory Response Syndrome

Галкин¹,

Demidova²

2015

jour

View full text Add to dashboard Cite

Regulation of Neutrophil Activation in Acute Lung Injury

Cited by 96 publications

References 56 publications

Differential Role of CD18 Integrins in Mediating Lung Neutrophil Sequestration and Increased Microvascular Permeability Induced byEscherichia coliin Mice

Differential Role of CD18 Integrins in Mediating Lung Neutrophil Sequestration and Increased Microvascular Permeability Induced byEscherichia coliin Mice

Surface expression of HSP72 by LPS‐stimulated neutrophils facilitates γδT cell‐mediated killing

Neutrophils and Systemic Inflammatory Response Syndrome

Contact Info

Product

Resources

About