The serum levels of
VEGF and PlGF in patients with
COPD (n = 184), smokers (n = 212) and non-smokers (n = 159) and the bronchoalveolar lavage (BAL) fluid levels of
VEGF and PlGF in another group (20 patients with
COPD, 18 controls) were measured. In vitro cell culture experiments were performed to investigate the effect of PlGF on
VEGF.
RESULTS: The mean (SE) serum levels of PlGF were significantly higher in patients with
COPD than in controls (27.1 (7.4) pg/ml vs 12.3 (5.1) pg/ml in smokers and 10.8 (6.3) pg/ml in non-smokers, p = 0.005). The levels of PlGF in BAL fluid were also significantly higher in patients with
COPD than in controls (45.7 (12.3) pg/ml vs 23.9 (7.6) pg/ml, p = 0.005), associated with an increase in the
cytokines tumour
necrosis factor-alpha (
TNF-alpha) and
interleukin-8 (IL-8). In patients with
COPD the levels of PlGF correlated inversely with forced expiratory volume in 1 s (FEV(1)) in serum (r = -0.59, p = 0.002) and in BAL fluid (r = -0.51, p = 0.001). While the serum levels of
VEGF were the same in patients with
COPD and controls, the BAL fluid levels were significantly lower in patients with
COPD than in controls (127.5 (30.1) pg/ml vs 237.8 (36.1) pg/ml, p = 0.002). In cultured bronchial epithelial cells, proinflammatory
cytokines induced an increase in the
protein expression of both PlGF and
VEGF. Continuous concomitant treatment with PlGF,
TNF-alpha and
IL-8 stimulation reduced
VEGF expression and induced cell death. This phenomenon was suppressed by
VEGF receptor inhibitor (CBO-P11).
CONCLUSIONS: The serum and BAL fluid levels of PlGF are increased in patients with
COPD and are inversely correlated with FEV(1). Concomitant treatment with PlGF,
TNF-alpha and
IL-8 causes detrimental effects on airway epithelial cells. These data suggest that bronchial epithelial cells can express PlGF, which may contribute to the pathogenesis of
COPD.