Tyrosine-specific protein kinase participates in the pathogenesis of acute immune complex alveolitis in rats.
Rabbit IgG antibodies against ovalbumin (OA) was injected intravenously into Wistar rats. When the animals were challenged with OA aerosolized by ultrasonic nebulization, acute lung injury occurred as reflected by increased recovery of bronchoalveolar cells, especially polymorphonuclear leukocytes (PMN) in bronchoalveolar lavage fluid (BALF). Lung morphology demonstrated cellular infiltration in the alveolar septa and intra-alveolar hemorrhage. When the rats were administered ST-638, a novel tyrosine kinase inhibitor, intraperitoneally prior to nebulization, the number of PMN in BALF decreased in a dose-dependent manner and superoxide anion (O2-)-producing activity in peripheral leukocytes was significantly suppressed. Furthermore, the reagent inhibited migration of human peripheral blood neutrophils induced by the chemotactic peptide f-met-leu-phe in vitro. These studies strongly indicate that tyrosine kinase plays an important role in immune complex-triggered neutrophil-related lung disorders, and the novel tyrosine kinase inhibitor ST-638 attenuates lung injury by preventing superoxide production and neutrophil migration.
Nomoto
Y
Y
Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Miyagawa
Y
Y
Shiraishi
T
T
Hirano
H
H
Kawasaki
M
M
Ogino
H
H
Furuno
T
T
Hagimoto
N
N
Hayashi
S
S
Yagawa
K
K
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D002934:Cinnamates / Q000494:pharmacology; D007105:Immune Complex Diseases / Q000276:immunology*; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011658:Pulmonary Fibrosis / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
D002934:Cinnamates; D013440:Sulfides; C060747:ST 638; D013481:Superoxides; D011505:Protein-Tyrosine Kinases