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

Neutrophils (PMNs) are considered key cellular mediators of sepsis ind uced acute lung injury. PMN activation is manifest by increased beta2 integrin expression and enhanced superoxide radical (O2-) generation. What is unclear is at which anatomical sites PMNs are activated and at which sites they release O2- and mediate lung injury. In this study w e compare alveolar (ALV), systemic arterial (SA), and pulmonary arteri al (PA) PMNs CD18 receptor expression, measured by fluorescent immunop henotyping and, O2- generation, measured by reduction of ferricytochro me C, in septic swine. Swine were anesthetized and ventilated, and giv en a 1-h infusion of live Pseudomonas aeruginosa. PA, SA, and ALV PMNs were isolated at 0 and 5 h. ALV PMNs O2- was reduced compared to SA b lood PMNs O2- at 5 h, (AIV 5 h 23.6 +/- 3 vs. SA 0 h 34.3 +/- 5, p < . 05). SA PMNs O2- 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 d ifferent from SA PMNs levels at 5 h. These data corroborate a dissocia tion between two PMN functions in sepsis. O2- generation was reduced a cross the lung and following migration. However, alveolar PMNs had sig nificantly upregulated CD18 expression compared to PMNs in PA and SA. These data suggest distinct PMN populations exist in sepsis, and distr ibution seems to depend on PMN CD18 expression. Thus, functional asses sment 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).