Relationship between granulocyte activation, pulmonary granulocyte kinetics and alveolar permeability in...

1. The aim of the study was to examine the relationship between granulocyte activation, pulmonary intravascular granulocyte transit, pulmonary extravascular granulocyte migration and lung injury in patients with systemic conditions (bone marrow transplant recipients, inflammatory bowel disease and systemic vasculitis) in which abnormalities of pulmonary granulocyte traffic have previously been reported. 2. A double 111In-99mTc granulocyte labelling technique was used for quantification of granulocyte kinetics in 23 patients, of whom five were control patients. The pulmonary vascular granulocyte pool was measured from dynamic data centred on the 99mTc signal and expressed as a percentage of the total blood granulocyte pool. Granulocyte migration was quantified on 24 h images using the 111In signal. Granulocyte activation was measured as the percentage of cells showing a change in shape. The clearance rate of an inhaled aerosol of 99mTc-diethylenetriaminepenta-acetic acid (DTPA) was used as a marker of lung injury. 3. Pulmonary granulocyte pool, migration, activation and aerosol clearance, although highly variable in the patient groups, were, in general, elevated compared with the controls. 4. Granulocyte activation correlated with pulmonary granulocyte pool (Rs = 0.72, n = 22, P < 0.01), while the t1/2 of DTPA clearance correlated with migration (Rs = -0.84, n = 17, P < 0.01). Fifteen patients had an expanded pulmonary granulocyte pool, of whom six with no evidence of migration, had a normal DTPA clearance, while nine, who had an abnormal migration signal, had an accelerated DTPA clearance. The pulmonary granulocyte pool in these nine was significantly higher than in the six without a migration signal. 5. Activation of granulocytes results in delayed transit through the lung vasculature. With increasing margination, granulocytes migrate into the lung interstitium and injure the lung. An increased intravascular pool does not by itself lead to lung injury.