Neutrophils from burn patients are unable to increase the expression of CD11b/CD18 in response to inflammatory stimuli

Rodeberg, David A.; Bass, R C; Alexander, J. Wesley; Warden, Glenn D.; Babcock, George F.

doi:10.1002/jlb.61.5.575

Cited by 32 publications

(19 citation statements)

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“…Taken together, these circumstances imply that diminished CD11b function is widespread in critically ill patients and may be a nonspecific effect of critical illness. A diminished quantitative CD11b up-regulation in response to mediators of inflammation has also been shown in burn patients [20].…”

Section: Discussionmentioning

confidence: 93%

Suppression of cytokine-mediated β2-integrin activation on circulating neutrophils in critically ill patients

Rosenbloom

Pinsky

Napolitano

et al. 1999

Journal of Leukocyte Biology

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The ␤ 2 integrin CD11b plays a central role in inflammation and the systemic inflammatory response syndrome (SIRS). The CD11b molecule activates in two ways: the density of membranebound CD11b up-regulates and the molecule undergoes a conformational change that confers adhesiveness to counter-receptors. We studied the kinetics of CD11b activation in patients with SIRS. We found a significantly diminished CD11b activation in response to tumor necrosis factor ␣ (TNF-␣). This affected all circulating polymorphonuclear neutrophils (PMN) and was an intrinsic property of the cells and not due to antagonism by soluble TNF-␣ receptors or loss of cellular receptors for TNF-␣. Diminished responsiveness correlated with the severity of organ failure and lasted for months in some patients but had no impact on mortality. We speculate that reduced CD11b responsiveness in SIRS contributes to the high risk of recurrent infection, but that it may also be protective against excessive PMN activation within the vascular space.

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Section: Discussionmentioning

confidence: 93%

Suppression of cytokine-mediated β2-integrin activation on circulating neutrophils in critically ill patients

Rosenbloom

Pinsky

Napolitano

et al. 1999

Journal of Leukocyte Biology

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“…These features might contribute to the decreased responses of PMNs in chemotaxis assays in vitro [70][71][72] and to the accumulation of PMNs in the pulmonary vasculature in vivo after thermal injury [73,74]. Increased expression of CD11b/CD18 occurs early (1-2 days) in burn patients [75], and PMNs become unresponsive to endotoxinstimulated CD11b/CD18 expression by 1 week after burn injury [76]. Thus, accumulated evidence indicates that endotoxemia occurs after thermal injury and that PMNs of burn victims have characteristics of endotoxic PMNs.…”

Section: Burn Patientsmentioning

confidence: 99%

“…Azurophilic and secretory granules in human PMNs store mCD14 and are mobilized to the cell membrane by activators such as fMLP and tumor necrosis factor ␣ (TNF-␣) as well as by LPS [76,116,117]. Similar responses in rodent PMNs have not been reported.…”

Section: Cd14 Receptor Bindingmentioning

confidence: 99%

Neutrophil migration during endotoxemia

Wagner

Roth

1999

Journal of Leukocyte Biology

177

125

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Endotoxemia is marked by a global activation of inflammatory responses, which can lead to shock, multiple organ failure, and the suppression of immune and wound healing processes. Neutrophils (PMNs) play a central role in some of these responses by accumulating in tissues and releasing reactive oxygen species and proteases that injure host structures. This review focuses on altered PMN migratory responses that occur during endotoxemia and their consequences in the development of pulmonary infection. The inflammatory mediators that might be responsible for these altered responses are discussed. The oxidant potential of PMNs is increased after exposure to endotoxin both in vitro and during clinical and experimental endotoxemia. However, other functions such as chemotaxis and phagocytosis are often depressed in these same cells. Endotoxin exposure renders PMNs hyperadhesive to endothelium. The sum of these effects produces activated inflammatory cells that are incapable of leaving the vasculature. As such, the endotoxic PMN is more likely to promote tissue injury from within microvascular beds than to clear pathogens from extravascular sites. Moreover, the functional characteristics of endotoxic PMNs are similar to those observed during trauma, burn injury, sepsis, surgery, and other inflammatory conditions. Accordingly, several clinical conditions might have a common effector in the activated, yet migratorially dysfunctional, PMN. Direct effects of endotoxin on PMNs as well as effects of endogenous mediators released during endotoxemia are discussed. Understanding PMN behavior during endotoxemia may provide basic and critical insights that can be applied to a number of inflammatory scenarios. J. Leukoc. Biol. 66: 10-24; 1999.

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“…Furthermore, numerous immunological alterations induced by burn injury impair innate and acquired immunities and decrease the ability of burn patients to control and eliminate infections. In both burned patients and animal models, NK cell, neutrophil, macrophage, and T cell functions are impaired (3)(4)(5)(6)(7)(8)(9)(10). Alterations in pathogen-elicited production of cytokines associated with Th1, Th2, and proinflammatory responses likely contribute to these global impairments (6,(11)(12)(13)(14)(15).…”

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confidence: 99%

Enhancement of Dendritic Cell Production by Fms-Like Tyrosine Kinase-3 Ligand Increases the Resistance of Mice to a Burn Wound Infection

Toliver‐Kinsky

Cui

Murphey

et al. 2005

The Journal of Immunology

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Fms-like tyrosine kinase-3 ligand (Flt3L) is a hemopoietic cytokine that stimulates the production of dendritic cells. This study evaluated the ability of Flt3L-enhanced dendritic cell production to increase the resistance of mice to a burn wound infection with Pseudomonas aeruginosa, a common source of infections in burn patients that have impaired immunity and are susceptible to opportunistic microorganisms. Treatment of mice with Flt3L for 5 days caused a significant increase in dendritic cell numbers in the spleen and significantly increased survival upon a subsequent burn wound infection. Improved survival in Flt3L-treated mice was associated with limited bacterial growth and spread within the burn wounds and a decrease in systemic dissemination of P. aeruginosa. Resistance to burn wound infection could also be conferred to recipient mice by the adoptive transfer of dendritic cells that had been isolated from spleens of Flt3L-treated mice. Adoptive transfer of the same number of splenic dendritic cells from nontreated mice did not confer resistance to burn wound infection. These data indicate that Flt3L can increase the resistance of mice to a P. aeruginosa burn wound infection through both stimulation of dendritic cell production and enhancement of dendritic cell function.

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Neutrophils from burn patients are unable to increase the expression of CD11b/CD18 in response to inflammatory stimuli

Cited by 32 publications

References 0 publications

Suppression of cytokine-mediated β2-integrin activation on circulating neutrophils in critically ill patients

Suppression of cytokine-mediated β2-integrin activation on circulating neutrophils in critically ill patients

Neutrophil migration during endotoxemia

Enhancement of Dendritic Cell Production by Fms-Like Tyrosine Kinase-3 Ligand Increases the Resistance of Mice to a Burn Wound Infection

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