Comparable effects of HOCl and of FMLP-stimulated PMN on the circulation in an isolated lung model.

Abstract

Polymorphonuclear leukocytes (PMN) are involved in acute lung injury during adult respiratory distress syndrome (ARDS) via several mechanisms. This study focuses on neutrophil-derived oxidative stress. The influence of (A), continuous hypochlorous acid (HOCl) infusion over 105 min and (B) stimulation of PMN having been delayed in the pulmonary microvasculature were studied. Therefore pulmonary artery pressure (PAP), capillary filtration coefficient (Kf,c), and fluid retention (delta W) were monitored using isolated rabbit lungs. These models (A/B) were compared with each other to assess the reproducibility of neutrophil-derived oxidative stress by HOCl. A: Infusion of 250/500/1,000/2,000 nmol/min HOCl (n = 6/group) evoked a delta PAPmax of 0.4 +/- 0.07/2.4 +/- 0.21/4.9 +/- 0.29/4.6 +/- 0.25 mm Hg at 105/105/56.4 +/- 5.6/21.5 +/- 0.8 min and a tenfold increase in Kf,c/delta W at 60 min. B: Stimulation of PMN (1,480 +/- 323/microliter, n = 8), which were added into the perfusate and sequestrated in the microvasculature, with 1 microM FMLP resulted in a delta PAPmax = 8.4 +/- 1.1 torr (t = 3.7 +/- 0.19 min) and a twofold increase in Kf,c/delta W (t = 60 min) that were accompanied by a myeloperoxidase (MPO)-release (MPOmax = 56.1 +/- 7.3 mU/l, after 1 to 3 min). There was a strong correlation between delta PAPmax and MPOmax (r = 0.97, p < 0.01). Both models of neutrophil-derived oxidative stress evoked changes in pulmonary circulation providing evidence for an involvement of PMN via their major oxidant HOCl in pulmonary hypertension and edema during ARDS.