RELATIONSHIP BETWEEN GRANULOCYTE ACTIVATION, PULMONARY GRANULOCYTE KINETICS AND ALVEOLAR PERMEABILITY IN EXTRAPULMONARY INFLAMMATORY DISEASE

1. The aim of the study was to examine the relationship between granul ocyte activation, pulmonary intravascular granulocyte transit, pulmona ry extravascular granulocyte migration and lung injury in patients wit h systemic conditions (bone marrow transplant recipients, inflammatory bowel disease and systemic vasculitis) in which abnormalities of pulm onary granulocyte traffic have previously been reported. 2. A double I n-111-Tc-99m granulocyte labelling technique was used for quantificati on of granulocyte kinetics in 23 patients, of whom five were control p atients, The pulmonary vascular granulocyte pool was measured from dyn amic data centred on the Te-99m signal and expressed as a percentage o f the total blood granulocyte pool, Granulocyte migration was quantifi ed on 24 h images using the In-111 signal, Granulocyte activation was measured as the percentage of cells showing a change in shape, The cle arance rate of an inhaled aerosol of Tc-99m-diethylenetriaminepenta-ac etic acid (DTPA) was used as a marker of lung injury. 3. Pulmonary gra nulocyte pool, migration, activation and aerosol clearance, although h ighly variable in the patient groups, were, in general, elevated compa red with the controls. 4. Granulocyte activation correlated with pulmo nary granulocyte pool (Rs=0.72, n=22, P<0.01), while the t(1/2) of DTP A clearance correlated with migration (Rs=-0.84, n=17, P<0.01), Fiftee n patients had an expanded pulmonary granulocyte pool, of whom six wit h no evidence of migration, had a normal DTPA clearance, while nine, w ho had an abnormal migration signal, had an accelerated DTPA clearance , The pulmonary granulocyte pool in these nine was significantly highe r than in the six without a migration signal. 5. Activation of granulo cytes results in delayed transit through the lung vasculature. With in creasing margination, granulocytes migrate into the lung interstitium and injure the lung, An increased intravascular pool does not by itsel f lead to lung injury.