{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:27:47Z","timestamp":1791325667835,"version":"4.3.1"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T00:00:00Z","timestamp":1233619200000},"content-version":"vor","delay-in-days":3931,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1998,5]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Expression of cell adhesion molecules (CAM) on the lung microvascular endothelium is believed to play a key role in the recruitment of leukocytes in pulmonary inflammation. Moreover, regulation of CAM expression may be an important mechanism through which this inflammation may be controlled. Experimental evidence has suggested that combined phosphodiesterase (PDE) 3 and 4 inhibitors increase cyclic AMP levels within cells greater than inhibition of either isoenzyme alone. In the present study we assessed the effect of combinations of rolipram (PDE4 inhibitor), ORG 9935 (PDE3 inhibitor) and salbutamol (\u03b2\u2010agonist) on CAM expression and neutrophil or eosinophil adhesion to human lung microvascular endothelial cells (HLMVEC).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Tumour necrosis factor\u2010\u03b1 (TNF\u2010\u03b1)\u2010induced intercellular adhesion molecule (ICAM)\u20101, vascular cell adhesion molecule (VCAM)\u20101 and E\u2010selectin expression were measured on HLMVEC monolayers at 6 h by a specific ELISA technique in the presence of different combinations of medium, rolipram, ORG 9935 and salbutamol.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Rolipram in combination with salbutamol, but neither agent alone, inhibited TNF\u2010\u03b1\u2010induced E\u2010selectin expression, whilst ICAM\u20101 and VCAM\u20101 expression were not affected. ORG 9935 had no significant effect on CAM expression alone. However, in combination with rolipram a syngergistic inhibition of VCAM\u20101 and E\u2010selectin, but not ICAM\u20101, expression was observed. No further inhibition was seen in the additional presence of salbutamol.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Neutrophil adhesion to TNF\u2010\u03b1\u2010stimulated (6 h) HLMVEC was mainly E\u2010selectin dependent in this model, as ENA<jats:sub>2<\/jats:sub> an anti\u2010E\u2010selectin monoclonal antibody (mAb) abrogated neutrophil adhesion. Eosinophil adhesion was E\u2010selectin\u2010, ICAM\u20101\u2010 and VCAM\u20101\u2010dependent, as assessed by the inhibitory activity of ENA<jats:sub>2<\/jats:sub> and the ability of a mAb to the ICAM\u20101 ligand, CD18, and a mAb to the VCAM\u20101 ligand, VLA<jats:sub>4<\/jats:sub>, to attenuate adhesion.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Rolipram in the presence of salbutamol or ORG 9935 significantly inhibited neutrophil adherence to TNF\u2010\u03b1\u2010stimulated HLMVEC. Eosinophil adherence to monolayers was inhibited only when HLMVEC were activated in the presence of rolipram and ORG 9935.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Collectively, the findings presented in this manuscript suggest that inhibition of PDE4 with appropriate activation of adenylate cyclase is sufficient to inhibit induction of E\u2010selectin expression on HLMVEC to a level that has functional consequences for neutrophil adhesion. In contrast, combined inhibition of PDE3 and 4 isoenzymes is necessary to inhibit VCAM\u20101 and to have inhibitory effects on eosinophil adhesion to activated HLMVEC. Upregulation of ICAM\u20101 expression on HLMVEC does not appear to be modulated by PDE3 and 4 inhibition. These data may have implications for the use of selective PDE4 inhibitors in lung inflammation.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p>","DOI":"10.1038\/sj.bjp.0701833","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:29:55Z","timestamp":1106940595000},"page":"229-237","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["Modulation of cell adhesion molecule expression and function on human lung microvascular endothelial cells by inhibition of phosphodiesterases 3 and 4"],"prefix":"10.1111","volume":"124","author":[{"given":"Kate","family":"Blease","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Burke\u2010Gaffney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul G","family":"Hellewell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,2,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830230925"},{"key":"e_1_2_6_3_1","first-page":"399","article-title":"Multiple cyclic nucleotide phosphodiesterases","volume":"46","author":"Beavo J.A.","year":"1994","journal-title":"Mol. 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