title: Phosphodiesterase type 4 inhibitor reduces the retention of polymorphonuclear leukocytes in the lung.
abstract: Phosphodiesterase (PDE) type 4 is the predominant PDE isozyme in polymorphonuclear leukocytes (PMN) and plays a key role in the regulation of PMN activation. The aim of this study was to examine the effect of a PDE type 4 inhibitor, rolipram, on the functional changes and the retention of PMN in the lung. In vitro, F-actin content and L-selectin and CD11b expression of PMN stimulated by N-formyl-Met-Leu-Phe were measured by flow cytometry. PMN deformability was evaluated using silicon microchannels. Rolipram reduced the increase of F-actin and CD11b but did not change the decrease of L-selectin. Rolipram inhibited the increase of the transit time of PMN through the microchannel. We evaluated the retention of PMN in the lung in vivo by infusing labeled blood into the vena cava and examining the recovery into aortic root samples in rabbits. Rolipram inhibited the retention of stimulated PMN in the lung. In conclusion, a PDE type 4 inhibitor, rolipram, reduces the retention of PMN in the lung by reducing deformability change and CD11b upregulation of PMN.
authors: Institute of Clinical Medicine, University of Tsukuba, Tsukuba, 305-8575 Japan. ysato@md.tsukuba.ac.jp
authors: Yukio
authors: Y
authors: Sato
authors: Shyoko
authors: S
authors: Sato
authors: Tatsuo
authors: T
authors: Yamamoto
authors: Shigemi
authors: S
authors: Ishikawa
authors: Masataka
authors: M
authors: Onizuka
authors: Yuzuru
authors: Y
authors: Sakakibara
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000199:Actins / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000502:physiology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D003584:Cytological Techniques / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004912:Erythrocytes / Q000502:physiology; D005260:Female; D006801:Humans; D019041:L-Selectin / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000166:cytology / Q000187:drug effects*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D018715:Microscopy, Video; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011652:Pulmonary Circulation / Q000502:physiology; D011817:Rabbits; D020889:Rolipram / Q000494:pharmacology*; D014684:Venae Cavae / Q000502:physiology
chemical_list: D000199:Actins; D004791:Enzyme Inhibitors; D016177:Macrophage-1 Antigen; D019041:L-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram