• Tuberculosis and Respiratory Diseases
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• v.43 no.2
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• pp.123-127
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• 1996

Secretion of surfactant phospholipid can be stimulated by a variety of agonists acting via at least three different signal transduction mechanisms. These include the adenylate cyclase system with activation of cAMP-dependent protein kinase; activation of protein kinase C either directly or subsequent to activation of phosphoinositide-specific phospholipase C and generation of diacylglycerols and inositol trisphosphate; and a third mechanism that involves incresed $Ca^{2+}$ levels and a calmodulin-dependent step. ATP stimulates secretion via all three mechanisms. The protein kinase C pathway is also coupled to phopholipase D which, acting on relatively abundant cellular phospholipids, generates diacylglycerols that further activate protein kinase C. Sustained protein kinase C activation can maintain phosphatidylcholine secretion for a prolonged period of time. It is likely that interactions between the different signaling pathways have an important role in the overall physiological regulation of surfactant secretion.

• Journal of Yeungnam Medical Science
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• v.1 no.1
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• pp.59-66
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• 1984

Although it is well established that steroid is effective for treatment of neonatal respiratory distress syndrome (NRDS), the action mechanism of steroid on NRDS is not well known. Several authors have insisted that steroid increases secretion of pulmonary surfactant from type II pneumocyte, but others have insisted that steroid does not affect the secretory function of the type II pneumocyte. And some authors have suggested that steroid may ca use compositional change of pulmonary surfactant phospholipid. From these aspects, it is desirable to confirm the effect of steroid on (he secretory function of the type II pneumocyte. In order to know the effect of steroid on pulmonary surfactant activity, phospholipid phosphorus of lung lavage was measured and composition of pulmonary surfactant phospholipid of lung lavage was analyzed by thin layer chromatography (TLC) in control (C), pneumonectomized (PN), and pneumonectomized with betamethasone treated (PNS) rabbits. And lung weight and lung weight-body weight ratio were measured in each experimental group also. In PN group, right lung pneumonectomy was performed under general anesthesia with pentobarbital sodium (30mg/kg). On the fifth day after the surgery, the left lung was excised and measured above parameters. In PNS group, pneumonectomy was performed as PN group, and one day after the surgery, betamethasone was injected for four days intramusculary (4mg/day) and rabbits were sacrificed. The experiment yielded following results. PNS group's lung weight was significantly (p<0.01) heavier than C group's, but in comparison with PN group's it showed no significant change. PNS group's L/B ratio was significantly (p<0.05) higher than C group's, but compared with PN group's it showed no significant change. The value of phospholipid phosphorus content of PNS group was significantly (p<0.01) higher than that of C group. Even if the value of phospholipid phosphorus content in PNS group was not significantly higher than that of PN group, it showed increasing tendency compared with that of PN group. And in an analysis of the thin layer chromatogram, quantity (${\mu}mol/gm$ of wet weight lung) of phosphatidylcholine in PNS group decreased significantly (p<0.05) compared with C and PN group. From these results, it may be suggested that though steroid inhibits cellular hyperplasia in the compensatory growing lung, it auguments the secretory function of type II pneumocyte and causes compositional change of pulmonary surfactant phospholipid.

• Tuberculosis and Respiratory Diseases
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• v.40 no.2
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• pp.91-97
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• 1993

Pulmonary surfactant is a lipoprotein complex composed primarily of phospholipid and lung specific apoproteins that reduces surface tension in the alveolus and maintains alveolar stability at low lung volume. Adult respiratory distress syndrome still carries a very high morbidity and mortality. The surfactant system is vital to the maintenance of proper lung function, any type of surfactant deficiency, whether primary or secondary, will contribute significantly to the development of pulmonary pathophysiology. Various mechanisms in adult respiratory distress syndrome may be responsible for such alterations in the surfactant system. Surfactant replacement is now an established treatment for neonatal respiratory distress syndrome, reducing both incidence of complications and mortality. With the current knowledge of surfactant physiology and the pathophysiology of the adult respiratory distress syndrome exogenous surfactant treatment or stimulation of endogenous surfactant synthesis and secretion will prove to be beneficial in preventing and treating the adult respiratory distress syndrome. The study of clinical surfactant therapy for adult respiratory distress syndrome is just beginnig and this can be viewed as an area with exciting potential. As soon as surfactant preparations become more widely available trials should begin to define the role of surfactant treatment in the adult respiratory distress syndrome as an adjunct to available treatment techniques.

• The Korean Journal of Physiology
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• v.25 no.1
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• pp.81-85
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• 1991

At the fifth day after right lung pneumonectomy in New-Zealand white rabbits $(0.8{\sim}1.1\;kg\;B.W.)$, phospholipid and protein concentration in the left lung lavage fluid were measured for clarification of the effect of unilateral pneumonectomy on the secretory function of the type II pneumocytes in growing rabbits. In an attempt to evaluate the effect of unilateral pneumonectomy on the compensatory growth of the residual lung, left lung weight and left lung weight-body weight ratio and DNA concentration, RNA/DNA and total DNA content in the left lung tissue were measured in pneumonectomized and in sham operated control rabbits. The lung weight of pneumonectomized rabbit was approximately two times heavier than that of the control rabbits. DNA concentration and RNA/DNA of the lung tissue were not changed but total DNA content was increased significantly. Phospholipid concentration in the lung lavage fluid of the pneumonectomized rabbits was over two times higher than that of control rabbits. from these experimental results, It is concluded that unilateral pneumonectomy in growing rabbits might cause to increase the secretion of pulmonary surfactant from type II pneumocyte of the residual lung. The cellular hyperplasia seems to be the primary response of the compensatory growing lung in unilateral pneumonectomized growing rabbits.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.925-935
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• 1996

Background : In order to elucidate one of the pathogenic mechanisms of ARDS associated with pulmonary surfactant and oxidant injury, acute lung injury was induced by N-nitroso N-methylurethane (NNNMU). In this model, the role of phospholipase $A_2$ ($PLA_2$), surfactant, gamma glutamyl transferase (GGT) and morphology were investigated to delineate one of the pathogenic mechanisms of ARDS by inhibition of $PLA_2$ with high dose of dexamethasone. Method: Acute lung injury was induced in Sprague-Dawley rats by NNNMU which is known to induce acute lung injury in experimental animals. To know the function of the alveolar type II cells, GGT activity in the lung and bronchoalveolar lavage was measured. Surfactant phospholipid was measured also. $PLA_2$ activity was measured to know the role of $PLA_2$ in ARDS. Morphological study was performed to know the effect of $PLA_2$ inhibition on the ultrastructure of the lung by high dose of dexamethasone. Results : Six days after NNNMU treatment (4 mg/kg), conspicuous pulmonary edema was induced and the secretion of pulmonary surfactant was decreased significantly. In the acutely injured rats' lung massive infiltration of leukocytes was observed. At the same time rats given NNNMU had increased $PLA_2$ and GGT activity tremendously. Morphological study revealed bizarre shaped alveolar type II cells and hypertrophied lamellar bodies in the cytoplasm of the alveolar type II cells. But after dexamethasone treatment (20 mg/kg, for six days) in NNNMU-treated rats, these changes were diminished i.e. there were decrease of pulmonary edema and increase of surfactant secretion from alveolar type D cells. Rats given dexamethasone and NNNMU had decreased $PLA_2$ and GGT activity in comparison to NNNMU induced ARDS rats. Conclusion : Inhibition of $PLA_2$ by high dose of dexamethasone decreased pathological findings caused by infiltration of leukocytes and respiratory burst. Based on these experimental results, it is suggested that an activation of $PLA_2$ is the one of the major factors to evoke the acute lung injury in NNNMU-induced ARDS rats.