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Arch Hellen Med, 28(5), September-October 2011, 680-689


Lung edema and thrombosis induced by activated mannose-binding lectinassociated serine protease 2
and MHC class I reactions, and liver thrombosis aggravated by suppressed phosphotyrosine and female donor reactions
to male-specific antigens in Lewis rats

T. Nakatsuji
Department of Transfusion Cell Therapy, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan

OBJECTIVE The causes of lung edema and thrombosis and liver embolism were investigated in rats.

METHOD Lewis rats were used. Mannose-binding lectin (MBL)-associated serine protease 2 (MASP-2) antibody (Ab) was injected to cause lung edema. Lung and liver thrombosis and embolism were generated using major histocompatibility complex (MHC) class I monoclonal Ab (mAb) and MASP-2 Ab. Liver embolisms and male-specific antigen reactions of minor histocompatibility antigens (mHA) were triggered by phosphotyrosine (pTyr) mAb. Correlative expressions of MASP-2 and pTyr were confirmed by flow cytometry (FCM).

RESULTS MASP-2 Ab caused acute intraalveolar and peribronchovascular edema, which was characterized by hemolytic red cell casts, type II cell activation with lamellar body (Lb) secretion and elevated apocrine secretion of Clara cells. MHC class I mAb and MASP-2 Ab caused severe lung and liver thrombosis and embolism. Immunochemically stained electron micrographs of alveolar type I cells showed a quick-activation of the second MASP-2, when the first MASP-2 was destroyed by MASP-2 Ab. In the liver injected with pTyr mAb, hepatocytes underwent selective apoptosis with Golgi apparatus disturbances. Liver thrombosis, which was aggravated by female donor immune rejections of male-specific mHA, was associated with hepatic venous dilatation. Heparin sodium accelerated lung surfactant (Lb) secretion. Exogenous chemotactic inhibitor suppressed cytokine-induced chemokines, which were triggered by pTyr mAb.

CONCLUSIONS Lung edema and thrombosis were caused by MASP-2 and MHC class I Abs. PTyr mAb injection accelerated liver thrombosis, based on tyrosine kinase disturbances, in which mHA immune reactions aggraved liver thrombosis.

Key words: Liver embolism, Lung edema, Lung thrombosis, Mannose-binding lectin, (MBL)-associated serine protease 2, Tyrosine kinase.

© Archives of Hellenic Medicine