Inhibition of PAF-induced expression of CD11b and shedding of L-selectin on human neutrophils and eosinophils by the type IV selective PDE inhibitor, rolipram

We quantitatively determined whether the selective phosphodiesterase (PDE) inhibitor, rolipram, inhibits changes in the adhesion molecules CD11b and L-selectin on platelet-activating factor (PAF)-stimulated human neutrophils and eosinophils in vitro. Incubations were performed in human whole blood obtained from healthy volunteers, to restrict activation by purification procedures and to simulate in vivo conditions, in which different cell types may interact, more closely. Receptor expression was measured after fixation of cells, using monoclonal antibodies and flow cytometry. Concentration-dependent inhibition of the PAF-induced CD11b expression and L-selectin shedding for neutrophils and eosinophils was observed with rolipram, dibutyryl cyclic adenosine monophosphate (cAMP), prostaglandin E2 (PGE2), and isoproterenol. However, these inhibitions did not exceed 50%. Preincubation with rolipram (10(-8) M) and subsequent incubation with isoproterenol (0.5x10(-8) M) or PGE2 (10(-8) M) induced a cumulative, but not synergistic, effect. Using the combination of rolipram with isoproterenol or PGE2, inhibition of PAF-induced L-selectin shedding from eosinophils was as high as 71+/-28 and 67+/-21%, respectively. Other inhibitions were below 50%. In conclusion, rolipram inhibits CD11b expression and L-selectin shedding of platelet-activating factor-stimulated neutrophils and eosinophils in whole blood in a concentration-dependent fashion. Inhibitions did not exceed 50%, even at high concentrations. The inhibition of platelet-activating factor induced shedding of L-selectin from eosinophils with a combination of rolipram and prostaglandin E2 or isoproterenol, however, was found to be approximately 70%. Inhibition of rolling adhesion of eosinophils may, therefore, be a mode of action of type IV phosphodiesterase inhibitors.

This article has been cited by other articles:

				M. J. Lorenowicz, M. Fernandez-Borja, and P. L. Hordijk cAMP Signaling in Leukocyte Transendothelial Migration Arterioscler. Thromb. Vasc. Biol., May 1, 2007; 27(5): 1014 - 1022. [Abstract] [Full Text] [PDF]

				A. Y. Meliton, N. M. Munoz, A. Lambertino, E. Boetticher, J. Learoyd, X. Zhu, and A. R. Leff Phosphodiesterase 4 inhibition of {beta}2-integrin adhesion caused by leukotriene B4 and TNF-{alpha} in human neutrophils Eur. Respir. J., November 1, 2006; 28(5): 920 - 928. [Abstract] [Full Text] [PDF]

				G. Monneret, S. Gravel, M. Diamond, J. Rokach, and W. S. Powell Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via a novel DP receptor Blood, September 15, 2001; 98(6): 1942 - 1948. [Abstract] [Full Text] [PDF]

				M. Aoki, S. Yamamoto, M. Kobayashi, K. Ohga, H. Kanoh, K. Miyata, K. Honda, and T. Yamada Antiasthmatic Effect of YM976, a Novel PDE4 Inhibitor, in Guinea Pigs J. Pharmacol. Exp. Ther., April 1, 2001; 297(1): 165 - 173. [Abstract] [Full Text]

				M. Aoki, M. Kobayashi, J. Ishikawa, Y. Saita, Y. Terai, K. Takayama, K. Miyata, and T. Yamada A Novel Phosphodiesterase Type 4 Inhibitor, YM976 (4-(3-Chlorophenyl)-1,7-diethylpyrido[2,3-d]pyrimidin-2(1H)-one), with Little Emetogenic Activity J. Pharmacol. Exp. Ther., October 1, 2000; 295(1): 255 - 260. [Abstract] [Full Text]

				M. A. Giembycz and M. A. Lindsay Pharmacology of the Eosinophil Pharmacol. Rev., June 1, 1999; 51(2): 213 - 340. [Abstract] [Full Text] [PDF]

				T. J. TORPHY Phosphodiesterase Isozymes . Molecular Targets for Novel Antiasthma Agents Am. J. Respir. Crit. Care Med., February 1, 1997; 157(2): 351 - 370. [Full Text]

				Y. Sato, S. Sato, T. Yamamoto, S. Ishikawa, M. Onizuka, and Y. Sakakibara Phosphodiesterase type 4 inhibitor reduces the retention of polymorphonuclear leukocytes in the lung Am J Physiol Lung Cell Mol Physiol, June 1, 2002; 282(6): L1376 - L1381. [Abstract] [Full Text] [PDF]