Y. Nomoto et al., TYROSINE-SPECIFIC PROTEIN-KINASE PARTICIPATES IN THE PATHOGENESIS OF ACUTE IMMUNE-COMPLEX ALVEOLITIS IN RATS, Respiration, 61(1), 1994, pp. 19-22
Rabbit IgG antibodies against ovalbumin (OA) was injected intravenousl
y into Wistar rats. When the animals were challenged with OA aerosoliz
ed by ultrasonic nebulization, acute lung injury occurred as reflected
by increased recovery of bronchoalveolar cells, especially polymorpho
nuclear leukocytes (PMN) in bronchoalveolar lavage fluid (BALF). Lung
morphology demonstrated cellular infiltration in the alveolar septa an
d intra-alveolar hemorrhage. When the rats were administered ST-638, a
novel tyrosine kinase inhibitor, intraperitoneally prior to nebulizat
ion, the number of PMN in BALF decreased in a dose-dependent manner an
d superoxide anion (O-2(-))-producing activity in peripheral leukocyte
s was significantly suppressed. Furthermore, the reagent inhibited mig
ration of human peripheral blood neutrophils induced by the chemotacti
c peptide f-met-leu-phe in vitro. These studies strongly indicate that
tyrosine kinase plays an important role in immune complex-triggered n
eutrophil-related lung disorders, and the novel tyrosine kinase inhibi
tor ST-638 attenuates lung injury by preventing superoxide production
and neutrophil migration.