1. Expression of cell adhesion molecules (CAM) on the lung microvascular endothelium is believed to play a key role in the recruitment of leukocytes in @entity55 . Moreover, regulation of CAM expression may be an important mechanism through which this @entity32 may be controlled. Experimental evidence has suggested that combined phosphodiesterase (PDE) 3 and 4 inhibitors increase @entity1919 levels within cells greater than inhibition of either isoenzyme alone. In the present study we assessed the effect of combinations of @entity7428 ( @entity1980 inhibitor), @entity56228 (PDE3 inhibitor) and @entity3045 (beta-agonist) on CAM expression and neutrophil or eosinophil adhesion to @entity1 lung microvascular endothelial cells (HLMVEC). 2. Tumour @entity39 factor-alpha ( @entity310 )-induced @entity2071 , @entity4725 and @entity4105 expression were measured on HLMVEC monolayers at 6 h by a specific ELISA technique in the presence of different combinations of medium, @entity7428 , @entity56228 and @entity3045 . 3. @entity7428 in combination with @entity3045 , but neither agent alone, inhibited @entity310 -induced @entity4105 expression, whilst @entity2071 and @entity4725 expression were not affected. @entity56228 had no significant effect on CAM expression alone. However, in combination with @entity7428 a syngergistic inhibition of @entity4725 and @entity4105 , but not @entity2071 , expression was observed. No further inhibition was seen in the additional presence of @entity3045 . 4. Neutrophil adhesion to @entity310 -stimulated (6 h) HLMVEC was mainly @entity4105 dependent in this model, as ENA2 an anti- @entity4105 monoclonal antibody (mAb) abrogated neutrophil adhesion. Eosinophil adhesion was @entity4105 -, @entity2071 - and @entity4725 -dependent, as assessed by the inhibitory activity of ENA2 and the ability of a mAb to the @entity2071 ligand, @entity1454 , and a mAb to the @entity4725 ligand, VLA4, to attenuate adhesion. 5. @entity7428 in the presence of @entity3045 or @entity56228 significantly inhibited neutrophil adherence to @entity310 -stimulated HLMVEC. Eosinophil adherence to monolayers was inhibited only when HLMVEC were activated in the presence of @entity7428 and @entity56228 . 6. Collectively, the findings presented in this manuscript suggest that inhibition of @entity1980 with appropriate activation of adenylate cyclase is sufficient to inhibit induction of @entity4105 expression on HLMVEC to a level that has functional consequences for neutrophil adhesion. In contrast, combined inhibition of @entity1980 isoenzymes is necessary to inhibit @entity4725 and to have inhibitory effects on eosinophil adhesion to activated HLMVEC. Upregulation of @entity2071 expression on HLMVEC does not appear to be modulated by @entity1980 inhibition. These data may have implications for the use of selective @entity1980 inhibitors in @entity55 .

Modulation of cell adhesion molecule expression and function on XXXX lung microvascular endothelial cells by inhibition of phosphodiesterases 3 and 4.

@entity1 :: ('9606', 'Species') :: ['human'] @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity1980 :: ('5141', 'Gene') :: ['PDE3 and 4', 'PDE4'] @entity7428 :: ('MESH:D020889', 'Chemical') :: ['Rolipram', 'rolipram'] @entity55 :: ('MESH:D011014', 'Disease') :: ['pulmonary inflammation', 'lung inflammation'] @entity39 :: ('MESH:D009336', 'Disease') :: ['necrosis'] @entity3045 :: ('MESH:D000420', 'Chemical') :: ['salbutamol'] @entity310 :: ('7124', 'Gene') :: ['TNF-alpha'] @entity4725 :: ('7412', 'Gene') :: ['vascular cell adhesion molecule (VCAM)-1', 'VCAM-1'] @entity56228 :: ('MESH:C097915', 'Chemical') :: ['ORG 9935'] @entity4105 :: ('6401', 'Gene') :: ['E-selectin'] @entity1919 :: ('MESH:D000242', 'Chemical') :: ['cyclic AMP'] @entity1454 :: ('3689', 'Gene') :: ['CD18'] @entity2071 :: ('3383', 'Gene') :: ['ICAM-1', 'intercellular adhesion molecule (ICAM)-1']
@entity1 :: (9606,Species) :: ['human']
