Objective: Polymorphonuclear neutrophils (PMN) are one of the major effecto
r cells of pulmonary defence against bacterial infection. To determine whet
her neutrophil function is impaired in patients with severe pneumonia, we a
ssessed the two main partial functions exocytosis and oxidative response (R
OS production) in isolated neutrophils from the peripheral venous blood of
pneumonia patients and healthy volunteers. In addition, pul monary neutroph
ils and peripheral neutrophils were compared in pneumonia patients.
Patients and methods: Twenty-one patients with severe pneumonia were enroll
ed in the study. Eleven patients were mechanically ventilated, ten patients
breathed spontaneously. For comparison, ten healthy adults were studied. T
he release of two markers of neutrophil exocytosis, lactoferrin and myelope
roxidase (MPO), with and without stimulation by phorbol-myristate-acetate:
(PMA), was determined using immunoluminometric assays. ROS production was q
uantified using luminol-enhanced chemiluminescence. In addition, the clinic
al severity of pneumonia was correlated to neutrophil exocytosis.
Results: With regard to blood neutrophils, both basal and PMA-stimulated ex
ocytosis were significantly impaired in pneumonia patients compared to heal
thy volunteers (basal lactoferrin secretion in pneumonia patients: 0.25 +/-
0.36 pg/PMN versus controls: 1.17 +/- 0.78 pg/PMN, p < 0.01). In contrast,
both basal and PMA-stimulated ROS production were increased in patients co
mpared to controls (spontaneous chemiluminescence in pneumonia patients: 13
.6 x 10(5) cpm versus controls: 5.5 x 10(5) cpm). In pneumonia patients, th
e pulmonary neutrophils released significantly more lactoferrin, MPO and RO
S compared to blood neutrophils (basal lactoferrin secretion of pulmonary n
eutrophils: 1.19 +/- 1.55 pg/PMN; p < 0,01). However, after stimulation wit
h PMA the exocytosis of pulmonary and blood neutrophils was similar. The se
verity of pneumonia and prognostic indices like albumin were inversely corr
elated to the release of lactoferrin in blood neutrophils (p < 0,05).
Conclusions: In patients with severe pneumonia, the exocytosis of blood neu
trophils was significantly impaired. In contrast to this, the oxidative res
ponse was increased. Impaired bone marrow maturation of neutrophils during
severe infection, perhaps due to shortened maturation time, could explain t
hese findings.