Ichiro Mochizuki

Pulmonary vascular involvement in sarcoidosis: granulomatous angiitis and microangiopathy in transbronchial lung biopsies.

To evaluate the occurrence of granulomatous angiitis and microangiopathy in the lung with sarcoidosis, transbronchial lung biopsy specimens were examined from 174 cases with sarcoidosis. Granulomatous angiitis was seen in 72 cases, which corresponded to 53% of the cases with granulomata. Granulomatous angiitis showed venous involvement (65%), both venous and arterial involvement (24%) or arterial involvement only (11%). There was no significant difference in occurrence of granulomatous angiitis between upper and lower lobes. The cases with granulomatous angiitis in the lung had a higher frequency of ophthalmic symptoms and elevated serum angiotensin converting enzyme level. Basal lamina layering in the microvasculature was more often observed in the bronchial mucosa than in the alveolar walls and is not exclusively related to granulomata. Endothelial proliferation and basal lamina alterations in granulomatous angiitis may be closely associated with granulomas. The present study revealed coexistence of granulomatous angiitis and microangiopathy in the lung with sarcoidosis and suggests that both may participate in the development of pulmonary sarcoidosis.

Changes in the peripheral vasculature of various organs in patients with sarcoidosis—Possible role of microangiopathy

SummaryVascular involvement in sarcoidosis is briefly reviewed with emphasis on the outcome of a 10-year project-study by the Sarcoidosis Research Committee of the Japanese Ministry of Health and Welfare. Examples of vascular disorder associated with sarcoidosis are presented, including basal lamina layering of the capillaries in the skeletal muscle, cardiac muscle, and lung, glomerulopathy in the kidney, vascular changes in the ocular fundus and bronchi, and impaired peripheral circulation that could be detected by thermography. According to our tentative definition, all of these disorders should be collectively called microangiopathy. The possible role of microangiopathy in the pathogenetic mechanism of sarcoidosis is also discussed. Although microangiopathy in sarcoidosis is a comprehensive term, it should be included, in addition to systemic granulomatous disease, as part of the clinicopathological entity of sarcoidosis.

Endothelial cell damage in sarcoidosis and neurosarcoidosis: autoantibodies to endothelial cells.

Damage to the vascular system, of which endothelial cells are the main constituent, may occur in sarcoidosis. Evidence of blood-brain barrier (BBB) disruption is shown in sarcoidosis with central nervous system (CNS) involvement by means of magnetic resonance imaging or computed tomography. We investigated the presence of antiendothelial cell antibodies by culture of endothelial cells derived from human umbilical cord vein and from human brain using an enzyme-linked immunosorbent assay, and the presence of circulating immune complexes using a Raji cell assay, in the sera of patients with sarcoidosis. The patients with sarcoidosis displayed significantly high levels of immunoglobulin G (IgG) binding to endothelial cells after blocking Fc receptor compared to controls (p < 0.01). The sera of neurosarcoid patients with CNS involvement still showed significantly increased levels of IgG binding to brain endothelial cells after blocking Fc receptor compared to controls and those of pulmonary sarcoidosis (p < 0.001 and p < 0.01 respectively). These results suggest that the presence of autoantibodies to endothelial cells may be involved in endothelial cell damage, including BBB disruption.

Relationship between mitochondria and the development of specific lipid droplets in capillary endothelial cells of the respiratory tract in patients with sarcoidosis.

The aim of this study was to morphologically evaluate damage in the capillary endothelial cells of the respiratory tract in patients with sarcoidosis. We examined tissues of the bronchus and lung obtained from 16 patients with sarcoidosis consisting of 2 stage 0, 10 stage I and 4 stage II patients, and 11 controls. The morphology of capillary endothelial cells was studied using electron microscopy. In the samples from patients with sarcoidosis, lipid droplets exhibiting dark monophasic density (unsaturated fatty acids) were surrounded by abundant lysosomes in the capillary endothelial cells, and the double-membrane structure of the mitochondria attached to these lipid droplets was lost in three cases. Biphasic lipid droplets with dark and lucent (saturated fatty acids) densities were also observed, accompanied by a few lysosomes containing the residual bodies of undigested lipid-containing substances. Lucent monophasic droplets were also detected in the tissues from patients with sarcoidosis. The plasma membrane was more often damaged in capillary endothelial cells containing biphasic lipid droplets, lucent monophasic droplets as well as in those with dark monophasic droplets. However, no lipid droplets were detected in capillary endothelial cells obtained from the control subjects, except in a single case. This study demonstrated that a large number of mitochondria were mobilized and showed notable morphological changes including swelling in the capillary endothelial cells in patients with sarcoidosis. A close relationship between mitochondria and lipid droplets was observed in capillary endothelial cells of the respiratory tract, and this relation may be involved in the pathogenesis of sarcoidosis.

EXPERIMENTAL STUDIES ON IMMUNOPATHOLOGY OF DISEASES OF RESPIRATORY TRACT

呼吸器についてのアレルギー性組織反応の惹起はこれまで主として抗肺抗体を用いた実験が報告されている.著者等は抗気道粘膜抗体の気道に対する影響を知る目的で抗気管・気管支粘膜血清を用いて気道のアレルギー性組織反応の惹起を試みた.すなわち抗家兎気管・気管支粘膜山羊血清を作製し, DEAE cellulose collumn chromatographyを用い,抗体価の高い分画を分離した.この分画をあらかじめ正常山羊血清で前処置した家兎に静脈内注射,気管支内注入を行ない,一部にはSO2吸入を併用し気管,気管支,肺の態度を病理組織学的に検討した.その結果気管および主気管支の粘膜固有層にfibrin染色陽性の細線維の増生が著明なものがみられた.また肺胞壁あるいは細気管支壁にマッソン体類似の芽状膨出物を認めた.これらの変化は主に抗気管・気管支粘膜抗体が関与した抗原抗体反応に基づく変化と考えた.