PENTOXIFYLLINE INHIBITS INTEGRIN-MEDIATED ADHERENCE OF INTERLEUKIN-2-ACTIVATED HUMAN PERIPHERAL-BLOOD LYMPHOCYTES TO HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS, MATRIX COMPONENTS, AND CULTURED TUMOR-CELLS

Peripheral blood lymphocytes (PBLs) cultured in the presence of recomb inant human interleukin-2 (rhIL-2) develop a natural killer (NK) cell phenotype (CD16(+), CD56(+), CD3(-)) and are referred to as lymphokine -activated killer cells (LAK). In developing the LAK phenotype, enhanc ed adherence to matrix components and endothelial cells have been desc ribed. In this report we investigated the functional behavior of adhes ion receptors in rhIL-2-activated PBLs by in vitro adhesion assay and by flow cytometry. Compared to PBLs, IL-2-activated PBLs had increased integrin-mediated adherence to: (1) fibronectin (FN), (2) human umbil ical vein endothelial (HUVE) cells, and (3) cultured melanoma and panc reatic tumor cell lines. This increase in adherence was mediated by in creased surface expression of members of the p, and p, integrin subfam ilies, as determined by flow cytometric analysis. No induction of an a ctivation-dependent beta(1) (CD29) epitope was detected. We also inves tigated the effects of the methylxanthine derivative pentoxifylline (P TX) on PBLs and rhIL-2-activated PBL adhesion. PBLs cocultivated in th e presence of rhIL-2 (1,000 U/mL) and PTX exhibited reduced adherence to FN, HUVE and cultured tumor cell lines. This inhibition by PTX was concentration and time-dependent. The increased expression of integrin s induced by rhIL-2 was only in part inhibited by PTX, suggesting that PTX induced a subpopulation of integrins that are expressed but funct ionally inactive. (C) 1994 by The American Society of Hematology.