Hepatocyte growth factor is produced by blood and alveolar neutrophils in acute respiratory failure

Abstract

We tested the novel hypothesis that neutrophils in the lung or the airspaces may produce hepatocyte growth factor (HGF) in ventilated patients with acute respiratory failure. Neutrophils were purified from blood and bronchoalveolar lavage (BAL) fluid samples from 16 mechanically ventilated patients who underwent BAL for a diagnostic workup of ventilator-acquired pneumonia. Most of the patients had pneumonia (n = 11). Ten nonventilated patients served as controls. Both blood and BAL neutrophils released HGF in vitro. Basal HGF secretion by blood neutrophils from controls was 823 (666) pg x ml(-1) x 10(-7) neutrophils (median, 25th-75th percentile) and doubled to 1,730 (1,684-2,316) pg x ml(-1) x 10(-7) neutrophils (P = 0.001) with lipopolysaccharide (LPS) stimulation. Basal HGF secretion by blood neutrophils from patients was similar [956 (655-2,140) pg x ml(-1) x 10(-7) neutrophils, P = 0.4] and doubled with LPS stimulation [2,767 (2,165-3,688) pg x ml(-1) x 10(-7) neutrophils, P < 0.0001 vs. controls]. Alveolar neutrophils released HGF in vitro [653 (397-1,209) pg x ml(-1) x 10(-7) neutrophils]. LPS stimulation did not significantly increase the HGF release from alveolar neutrophils [762 (434-1,305) pg x ml(-1) x 10(-7) neutrophils]. BAL HGF positively correlated with the BAL neutrophil count (P = 0.01, R = 0.58). We conclude that blood and alveolar neutrophils from patients with acute respiratory failure can produce HGF, a mitogenic factor that may enhance the alveolar repair process.