title: Beta2-integrin adhesion caused by eotaxin but not IL-5 is blocked by PDE-4 inhibition and beta2-adrenoceptor activation in human eosinophils.
abstract: We investigated the effect and mechanism(s) of PDE-4 treatment with concurrent beta2-adrenoceptor stimulation on human eosinophil adhesion mediated by beta2-integrin in vitro. Eosinophils were pretreated with either rolipram, a PDE-4 inhibitor, alone or combined with salmeterol, a beta2-adrenoceptor agonist, before activation with either eotaxin or IL-5. Beta2-integrin mediated adhesion was assessed as adherence to BSA, an established surrogate for ICAM-1. Rolipram caused progressive blockade (77.7 +/- 6.2%) of adhesion elicited by eotaxin. Maximal blockade of IL-5-activated adhesion by rolipram was substantially less (29.9 +/- 5.2%). Salmeterol + rolipram synergistically enhanced the blockade of eotaxin-activated adhesion. Eotaxin also caused approximately 50% increase in surface CD11b expression, which was blocked additively by rolipram + salmeterol. By contrast, CD11b upregulation caused by IL-5 was not blocked by rolipram + salmeterol. Rolipram also attenuated cPLA2 phosphorylation caused by eotaxin but did not block IL-5-induced phosphorylation. We conclude that rolipram blocks expression of CD11b and inhibits cPLA2 phosphorylation in human eosinophils, thus blocking eotaxin-induced adhesion of beta2-integrin. IL-5-induced adhesion likely utilizes a different upstream mechanism in regulation of integrin adhesion.
authors.affiliation: Section of Pulmonary and Critical Care Medicine, Department of Medicine MC6076, The University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Nilda M
authors.initials: NM
authors.lastname: Muñoz
authors.forename: Angelo Y
authors.initials: AY
authors.lastname: Meliton
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Zhu
authors.forename: Anissa T
authors.initials: AT
authors.lastname: Lambertino
authors.forename: Chang
authors.initials: C
authors.lastname: Xu
authors.forename: Saori
authors.initials: S
authors.lastname: Myo
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Myou
authors.forename: Evan
authors.initials: E
authors.lastname: Boetticher
authors.forename: Malcolm
authors.initials: M
authors.lastname: Johnson
authors.forename: Alan R
authors.initials: AR
authors.lastname: Leff
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D039481:CD11b Antigen / Q000096:biosynthesis; D018821:CD18 Antigens / Q000096:biosynthesis / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000494:pharmacology* / Q000502:physiology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004357:Drug Synergism; D004789:Enzyme Activation; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D054513:Group IV Phospholipases A2; D006801:Humans; D066298:In Vitro Techniques; D015848:Interleukin-5 / Q000494:pharmacology* / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D020889:Rolipram / Q000494:pharmacology; D000068299:Salmeterol Xinafoate; D015854:Up-Regulation
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; C515456:CCL11 protein, human; D039481:CD11b Antigen; D018821:CD18 Antigens; D054413:Chemokine CCL11; D019742:Chemokines, CC; D015848:Interleukin-5; D010726:Phosphodiesterase Inhibitors; D000068299:Salmeterol Xinafoate; D010741:Phospholipases A; D054513:Group IV Phospholipases A2; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram; D000420:Albuterol