DIFFERENTIAL ACTIVATION OF ALVEOLAR, PULMONARY ARTERIAL, AND SYSTEMIC ARTERIAL NEUTROPHILS DEMONSTRATES THE EXISTENCE OF DISTINCT NEUTROPHIL SUBPOPULATIONS IN EXPERIMENTAL SEPSIS

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Abstract

ABSTRACT

Neutrophils (PMNs) are considered key cellular mediators of sepsis induced acute lung injury. PMN activation is manifest by increased β2 integrin expression and enhanced superoxide radial (O-2) generation. What is unclear is at which anatomical sites PMNs are activated and at which sites they release O-2 and mediate lung injury. In this study we compare alveolar (ALV), systemic arterial (SA), and pulmonary arterial (PA) PMNs CD18 receptor expression, measured by fluorescent immunophenotyping and, O-2 generation, measured by reduction of ferricytochrome C, in septic swine. Swine were anesthetized and ventilated, and given a 1-h infusion of live Pseudomonas aeruginosa. PA, SA, and ALV PMNs were isolated at 0 and 5 h. ALV PMNs O-2 was reduced compared to SA blood PMNs O-2 at 5 h, (AIV 5 h 23.6 ± 3 vs. SA 0 h 34.3 ± 5, p < .05). SA PMNs O-2 generation was also significantly reduced compared to PA PMNs at 5 h (PA 5 h 21 ± 2.5 vs. SA 5 h 16.9 ± 2.6, p < .05). Alv PMNs expressed significantly greater CD18 receptor levels than SA blood PMNs at 5 h (AIV PMNs 5 h, 76 ± 6 vs. SA PMNs 5 h 51 ± 3, p < .05), however, PA PMNs CD18 receptor levels were not significantly different from SA PMNs levels at 5 h. These data corroborate a dissociation between two PMN functions in sepsis. O-2 generation was reduced across the lung and following migration. However, alveolar PMNs had significantly upregulated CD18 expression compared to PMNs in PA and SA. These data suggest distinct PMN populations exist in sepsis, and distribution seeems to depend on PMN CD18 expression. Thus, functional assessment of circulating cells may not reflect the true ability of PMNs to mediate host tissue injury (versus time, 0 h; versus mixed venous, p < .05).

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