Phosphodiesterase type 4 inhibitor reduces the retention of polymorphonuclear leukocytes in the lung.
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.
Sato
Yukio
Y
Institute of Clinical Medicine, University of Tsukuba, Tsukuba, 305-8575 Japan. ysato@md.tsukuba.ac.jp
Sato
Shyoko
S
Yamamoto
Tatsuo
T
Ishikawa
Shigemi
S
Onizuka
Masataka
M
Sakakibara
Yuzuru
Y
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
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