Relationship of Alveolar Macrophage Plasminogen Activator and Elastase Activities to Lung Function and CT Evidence of Emphysema

¹ From the Respiratoiy Division, Department of Medicine, University of British Columbia, Vancouver Hospital and Health Sciences Centre, Vancouver, BC, Canada
² From the Respiratoiy Division, and the Department of Radiology, Vancouver Hospital and Health Sciences Centre, Vancouver, BC, Canada

Objective: To evaluate the relationship between alveolar macrophage (AM) elastase and plasminogen activator (PA) activities (considered to be potential pathogenetic factors in emphysema) and the development of emphysema in smokers.

Participants: Thirty-four healthy smokers >35 years of age (mean±SD, 46±7 years), with a mean±SD of 33±10 pack-years of smoking, who were recruited as volunteers.

Methods: Subjects had lung function testing and BAL to obtain AMs; limited high-resolution CT scans of the chest were obtained in 32 subjects to assess the presence of emphysema. Macrophage PA and elastase were determined using AM cultured on ¹³¹I-fibrin-coated plates and ³H-elastincoated plates, respectively.

Results: The number of AMs recovered per milliliter of BAL was significantly greater in the 16 subjects with CT evidence of mild emphysema than the 16 subjects without evidence of emphysema (669±301x10³/mL vs 414±268x10³/mL; p=0.01). There was no significant difference between AM elastase or PA activities in the 16 subjects with CT evidence of mild emphysema, when compared with the 16 subjects who had no CT evidence of emphysema (elastase, 2.72±1.35 µg vs 2.49±0.91 µg elastin per 10⁶ AMs per first 24 h; PA, 0.375±0.126 vs 0.344±0.096 urokinase units/10⁶ AMs). There was no significant correlation between levels of PA or elastase activities and FEV₁, FEV₁/FVC, forced expiratory flow rate between 25% and 75% of the FVC; PA activity but not elastase activity had a significant negative correlation (r=0.47, p<0.01) with diffusion of carbon monoxide (DCO). The macrophage count in BAL had a significant negative correlation with DCO percent predicted (r=0.61, p<0.001).

Conclusions: The findings suggest that the number of AMs recovered per milliliter of BAL (presumably indicating the number in the alveolar spaces) is related to the development of emphysema in smokers as indicated by CT scan of the chest and DCO. The results also suggest that the level of PA enzyme activity in AMs may be a pathogenetic factor in the decrease in DCO in smokers.

Key Words: alveolar macrophages • bronchoalveolar lavage • CT scan of the chest • emphysema • macrophage elastase • macrophage plasminogen activator • smoking

Submitted on November 8, 1996
Accepted on October 31, 1997

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