ALTERATIONS IN L-SELECTIN EXPRESSION AND ELASTASE ACTIVITY IN NEUTROPHILS FROM PATIENTS RECEIVING GRANULOCYTE-COLONY-STIMULATING FACTOR ALONE OR IN CONJUNCTION WITH HIGH-DOSE CHEMOTHERAPY WITH AUTOLOGOUS BONE-MARROW TRANSPLANTATION

We determined L-selectin expression and elastase levels in neutrophils obtained from patients receiving granulocyte colony-stimulating facto r (G-CSF) either alone (given for increasing peripheral progenitor cel ls for harvest) or in combination with high-dose chemotherapy with aut ologous bone transplantation support (BMT). Administration of G-CSF al one for 3-5 days produced a decrease in L-selectin expression in neutr ophils (25 +/- 4 versus 7 +/- 1, mean +/- SEM; mean channel fluorescen ce, n = 10) with no effect on nentrophil elastase activity (3.1 +/- 0. 3 versus 3.4 +/- 0.6; mu g elastase/million cells; n = 9). In contrast , in patients in the BMT group the L-selectin expression was increased (26 +/- 2 versus 38 +/- 3; n = 20) and elastase activity was markedly decreased (2.9 +/- 0.2 versus 1.4 +/- 0.2, n = 12) compared with valu es before BMT. The changes in L-selectin expression correlated with th e ability of neutrophils to adhere to human umbilical vein endothelial cells. The decrease in the neutrophil elastase activity was not assoc iated with an increase in the plasma elastase/alpha(1)-antitrypsin com plex levels, indicating that the decrease in the neutrophil elastase a ctivity is not caused by activation of neutrophils and release of the enzyme into the plasma. Administration of G-CSF alone did not cause a decrease in the neutrophil elastase activity but increased plasma elas tase/alpha(1)-antitrypsin complex levels. There was no change in CR3 e xpression on neutrophils under any of these conditions. These observat ions suggest that the changes seen in neutrophils during BMT are influ enced by various factors associated with BMT other than the administer ed cytokine alone. Perhaps production of endogenous cytokines plays an important role in these changes. Understanding these molecular change s and the roles played by various factors in these changes is essentia l for devising methods for reducing the toxicity associated with treat ment protocols using various biologic modifiers.