Journal of Nippon Medical School: Vol.67 No.2 page.118

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ArticleTitle Heterogeneous Distribution of Thrombomodulin and von Willebrand Factor in Endothelial Cells in the Human Pulmonary Microvessels

AuthorList Oichi Kawanami¹, Enjing Jin¹, Mohammad Ghazizadeh¹, Masakazu Fujiwara¹, Li Jiang¹, Mikio Nagashima¹, Hajime Shimizu¹, Tamiko Takemura², Yoshiharu Ohaki³, Satoru Arai³, Makoto Gomibuchi⁴, Kazuyo Takeda⁵, Zu-Xi Yu⁵ and Victor J. Ferrans⁵

Affiliation ¹Department of Molecular Pathology, Institute of Gerontology, Nippon Medical School, Japan ²Department of Pathology, Nippon Red Cross Hospital Center, Japan ³Surgical Pathology, and ⁴Surgery Sections, Hokusoh Hospital, Nippon Medical School, Japan ⁵Pathology Section, National Heart, Lung and Blood Institute, National Institutes of Health, USA

Language EN

Volume 67

Issue 2

Year 2000

Page 118-125

Received December 10, 1999

Accepted December 28, 1999

Keywords pulmonary microvessel, endothelial cells, confocal microscopy, thrombomodulin, von Willebrand factor

Abstract Laser scanning confocal fluorescence microscopy techniques were used to study the localization of von Willebrand factor (vWf; Factor VIII-related antigen) and thrombomodulin (transmembrane receptor for thrombin) in the microvascular endothelial cells in the normal human lung. Tissues were obtained from lobectomy specimens resected for solitary nodules (7 adenocarcinomas and 4 hamartomas) from 11 patients. The plasma membranes of the capillary endothelial cells in the alveolar zones (A-zones) showed red linear fluorescence for thrombomodulin. However, their cytoplasm was mostly unreactive for vWf. The microvessels which were located in the connective tissue (C-zones) , including peribronchial, and subpleural areas and large vascular walls, consistently demonstrated band-like green fluorescence for vWf in their cytoplasm, and their plasma membranes usually lacked reactivity for thrombomodulin. Only a limited number of peribronchial capillaries measuring<10μm in diameter showed a mosaic-like appearance, in which red fluorescence along the plasma membranes was found together with green fluorescence in the subjacent cytoplasm. In the juxtaalveolar (J-zones) microvessels located along the borders between A-and C-zones, and measuring up to 40μm in diameter, the endothelial cells showed a mosaic-like pattern of distribution of the two antigens. However, the localization of thrombomodulin in the J-zone microvessels was separate and independent from that of vWf. The thrombomodulin-reactive cells were directly connected to the alveolar capillary endothelial cells. Heterogeneous patterns of distribution of thrombomodulin and vWf suggest that topographic differences of endothelial function occur to maintain a balance of coagulation and anticoagulation in the normal human lung.

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ArticleTitle	Heterogeneous Distribution of Thrombomodulin and von Willebrand Factor in Endothelial Cells in the Human Pulmonary Microvessels
AuthorList	Oichi Kawanami¹, Enjing Jin¹, Mohammad Ghazizadeh¹, Masakazu Fujiwara¹, Li Jiang¹, Mikio Nagashima¹, Hajime Shimizu¹, Tamiko Takemura², Yoshiharu Ohaki³, Satoru Arai³, Makoto Gomibuchi⁴, Kazuyo Takeda⁵, Zu-Xi Yu⁵ and Victor J. Ferrans⁵
Affiliation	¹Department of Molecular Pathology, Institute of Gerontology, Nippon Medical School, Japan ²Department of Pathology, Nippon Red Cross Hospital Center, Japan ³Surgical Pathology, and ⁴Surgery Sections, Hokusoh Hospital, Nippon Medical School, Japan ⁵Pathology Section, National Heart, Lung and Blood Institute, National Institutes of Health, USA
Language	EN
Volume	67
Issue	2
Year	2000
Page	118-125
Received	December 10, 1999
Accepted	December 28, 1999
Keywords	pulmonary microvessel, endothelial cells, confocal microscopy, thrombomodulin, von Willebrand factor
Abstract	Laser scanning confocal fluorescence microscopy techniques were used to study the localization of von Willebrand factor (vWf; Factor VIII-related antigen) and thrombomodulin (transmembrane receptor for thrombin) in the microvascular endothelial cells in the normal human lung. Tissues were obtained from lobectomy specimens resected for solitary nodules (7 adenocarcinomas and 4 hamartomas) from 11 patients. The plasma membranes of the capillary endothelial cells in the alveolar zones (A-zones) showed red linear fluorescence for thrombomodulin. However, their cytoplasm was mostly unreactive for vWf. The microvessels which were located in the connective tissue (C-zones) , including peribronchial, and subpleural areas and large vascular walls, consistently demonstrated band-like green fluorescence for vWf in their cytoplasm, and their plasma membranes usually lacked reactivity for thrombomodulin. Only a limited number of peribronchial capillaries measuring<10μm in diameter showed a mosaic-like appearance, in which red fluorescence along the plasma membranes was found together with green fluorescence in the subjacent cytoplasm. In the juxtaalveolar (J-zones) microvessels located along the borders between A-and C-zones, and measuring up to 40μm in diameter, the endothelial cells showed a mosaic-like pattern of distribution of the two antigens. However, the localization of thrombomodulin in the J-zone microvessels was separate and independent from that of vWf. The thrombomodulin-reactive cells were directly connected to the alveolar capillary endothelial cells. Heterogeneous patterns of distribution of thrombomodulin and vWf suggest that topographic differences of endothelial function occur to maintain a balance of coagulation and anticoagulation in the normal human lung.
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