Pulmonary granulocyte kinetics in relation to endothelial and granulocyte activation

The aim of the study was to measure the peripheral blood levels of soluble E-selectin in patients with systemic inflammation and compare them with in vivo granulocyte activation, pulmonary intravascular granulocyte pooling, p ulmonary extravascular granulocyte migration and Tc-99m-diethylenetriaminep enta-acetic acid (DTPA) aerosol clearance, an index of lung injury. The lev el of soluble E-selectin was measured by capture ELISA. Granulocytes were l abelled with In-111 and Tc-99m for quantification of pulmonary granulocyte kinetics. The pulmonary vascular granulocyte pool (PGP) was expressed as a fraction of the total blood granulocyte pool. Pulmonary granulocyte migrati on was quantified on 24-h images using the In-111 signal. Granulocyte activ ation was quantified as the percentage of circulating cells showing shape c hange ('primed'). Lung injury was assessed from the clearance rate of inhal ed Tc-99m-DTPA aerosol. Eighteen patients with systemic inflammation were s tudied: five with inflammatory bowel disease, eight with systemic vasculiti s, four with graft versus host disease and one with a recent renal transpla nt. The peripheral blood levels of soluble E-selectin were significantly el evated in patients with systemic inflammation. The level of soluble E-selec tin showed a significant association with granulocyte migration (Spearman r ank correlation coefficient, Rs = 0.53; P < 0.05) but not with PGP or with the percentage of cells showing shape change (P > 0.05 for both). Granulocy te migration was bimodal: patients were therefore subdivided into 'migrator s' and non-migrators'. Soluble E-selectin level, 99mTc-DTPA clearance and P GP, but not the percentage of cells showing shape change, were significantl y higher in migrators than in non-migrators. We conclude that pulmonary int ravascular granulocyte pooling is increased in the presence of increased nu mbers of circulating primed granulocytes but increased pooling does not by itself promote granulocyte migration into the lung interstitium. Insofar as an elevated level of E-selectin in peripheral blood reflects vascular endo thelial activation, the data are consistent with the notion that pulmonary endothelial activation is required, in addition to granulocyte activation a nd an expanded PGP, for granulocyte migration into lung parenchyma and, the refore, for lung injury to occur.