Postinjury Neutrophil Priming and Activation States

Complement-Induced Impairment of Innate Immunity During Sepsis

“…In the early period (Ͻ24 hour) following trauma, burn injury, or sepsis, neutrophils have been reported to be "primed" and hyperactive (on the basis of in vitro stimulation) potentially putting patients at increased risk of neutrophil-mediated tissue injury (3,4,8). At later time points (48 h), neutrophils are unresponsive to activation and exhibit a variety of depressed functions: chemotactic responses (3,4,10,16), enzyme release (3,4), microtubular reorientation (26), phagolysosomal acidification (11), and respiratory burst activity (3, 4, 8, 9, 13-15).…”

“…At later time points (48 h), neutrophils are unresponsive to activation and exhibit a variety of depressed functions: chemotactic responses (3,4,10,16), enzyme release (3,4), microtubular reorientation (26), phagolysosomal acidification (11), and respiratory burst activity (3, 4, 8, 9, 13-15). Collectively, this compromise of innate immunity leads to a loss of oxygen-dependent bacterial killing, causing these individuals to be at high risk for bacterial infections (3,4,8). The mechanisms involved in sepsisinduced neutrophil dysfunction are poorly understood, precluding definitive specific therapeutic interventions.…”

“…Such perturbations occur in humans and in experimental models of sepsis (5,6). During sepsis in humans, unregulated activation of the complement system results in excessive generation of anaphylatoxins, especially C3a and C5a (4,7), and ensuing dysfunction of neutrophils (3,4,8,9). In later stages of sepsis, neutrophils have suppressed chemotactic responsiveness (3,4,10), depressed enzyme release (3,4,8,9), alterations of intracellular pH (11), and a defective respiratory burst (diminished production of reactive oxygen species, especially H 2 O 2 ) (3,4,12,13), collectively leading to impaired bactericidal activity.…”

“…During sepsis in humans, unregulated activation of the complement system results in excessive generation of anaphylatoxins, especially C3a and C5a (4,7), and ensuing dysfunction of neutrophils (3,4,8,9). In later stages of sepsis, neutrophils have suppressed chemotactic responsiveness (3,4,10), depressed enzyme release (3,4,8,9), alterations of intracellular pH (11), and a defective respiratory burst (diminished production of reactive oxygen species, especially H 2 O 2 ) (3,4,12,13), collectively leading to impaired bactericidal activity. Neutrophils from healthy human volunteers incubated with plasma from patients with sepsis or severe trauma have exhibited suppressed superoxide (O 2 Ϫ ) production (7,14,15), suggesting that a plasma factor may be responsible for suppression of the respiratory burst.…”

Rutin Ameliorates Neutrophilic Oxidative Stress-Induced Acute Lung Injury by Intratracheal IL-1 Insufflation in Rats

“…For cytochrome-c reduction assay, save control samples, phorbol myristate acetate (PMA, 2.5 μ g/ml), rutin (100 μM), manoalide (20 μM), scalaladial (200 μM) were added to the neutrophil suspension (2×10 6 cell/ml) before incubating for 15 min at 37 o C. Additionally, to know the effect of group II PLA2 on the generation of free radicals from neutrophils, Crotalus adamanteus PLA2 (1.0 unit) was added to the neutrophil suspension before incubat- ing for 60 min at 37 o C. Rutin was added to know the effect on the generation of free radicals in PLA2-stimulated neutrophils. Light absorbance at 550 nm was proportional to the reduction of cytochrome-c by free radicals [2,8].…”