DEFORMABILITY AND CD11/CD18 EXPRESSION OF SEQUESTERED NEUTROPHILS IN NORMAL AND INFLAMED LUNGS

Neutrophil (PMN) sequestration in the pulmonary microvasculature precedes the migration of these cells into the airspaces in inflamed lungs, Intratracheal instillation of the heat-killed organism Corynebacterium parvum in the rat induces an alveolitis in which PMN constitute 70 to 80% of the total cell count in the bronchoalveolar lavage (BAL). This acute alveolitis results in increased sequestration in the pulmonary microvasculature of Cr-51-labeled PMN when compared with control lungs. The aims of this study were to confirm this increased pulmonary PMN sequestration using unlabeled cells and to assess the function and adhesion molecule expression of such sequestered PMN. We counted the number of PMN and erythrocytes obtained by pulmonary vascular lavage (PVL) and compared the ratio of these two cell types in PVL and peripheral blood (PB) as a measure of the sequestration of PMN in the pulmonary vasculature. Compared with control animals, PVL in C, parvum-treated rats had higher PMN counts, which could not be accounted for by the PB leukocytosis. Sequestration of PMN in the pulmonary microvasculature depends on several factors, including the upregulation of adhesion molecules on both PMN and endothelial surfaces and the ability of the cells to deform when passing through the microcirculation, Cells obtained from the PVL were less deformable than PB cells in control but not in C, parvum-treated animals. The expression of the CD18 integrin on PMN obtained from the PVL of C, parvum-treated animals was increased compared with cells from control animals, PMN priming was assessed as the ability of PB, PVL, and BAL PMN to release superoxide anion (O-2(-)) before and after stimulation with phorbol myristate acetate (PMA), O-2(-) production from PB and PVL PMN of control rats was similar both for the spontaneous release and the increased release after stimulation with PMA. PVL PMN from C, parvum-treated rats tended to have higher spontaneous O-2(-) production than PMN obtained from the PVL in control animals or from PB in C, parvum-treated rats. However, PVL PMN from C, parvum-treated rats showed substantially increased O-2(-) production when stimulated with PMA, compared with similar treatment of control cells. BAL PMN produced similar amounts of Or after PMA as those from PB PMN from C, parvum-treated rats. These data support the hypothesis that PMN sequestration in the pulmonary microvasculature in this model of acute alveolitis is associated with a change in PMN CD11/CD18 adhesion molecules, whereas in control animals cell deformability rather than changes in adhesion molecules is associated with the normal PMN sequestration in the lungs. Furthermore, sequestered PMN are primed to release oxygen radicals in this model.