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Published ahead of print on January 30, 2004, doi:10.1164/rccm.200308-1111OC

Am. J. Respir. Crit. Care Med., Volume 169, Number 11, June 2004, 1203-1208

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Submitted on September 12, 2003
Accepted on January 26, 2004

Heterogeneous Increase of CD34-positive Alveolar Capillaries in Idiopathic Pulmonary Fibrosis

Masahito Ebina1*, Minoru Shimizukawa1, Naoko Shibata1, Yuichiro Kimura1, Takashi Suzuki2, Mareyuki Endo2, Hironobu Sasano2, Takashi Kondo3, and Toshihiro Nukiwa1

1 Respiratory Oncology and Molecular Medicine, Tohoku University, Institute of Development, Aging and Cancer, Sendai, Miyagi, Japan, 2 Pathology, Tohoku University School of Medicine, Sendai, Miyagi, Japan, 3 Thoracic Surgery, Institute of Development, Aging and Cancer, Sendai, Miyagi, Japan

* To whom correspondence should be addressed. E-mail: ebinam{at}idac.tohoku.ac.jp.

To elucidate the apparent contradictions in vascular remodeling in the lungs of patients with idiopathic pulmonary fibrosis, we evaluated the alveolar vascularity in relation to the various degrees of fibrosis in surgically biopsied lungs of usual interstitial pneumonia. The alveolar capillary endothelial cells were intensely immunoreactive with CD34 but not with von Willebrand factor (vWF). The vascular density, the relative ratio of the capillary area to the total area of alveolar walls, was significantly higher at low grades of fibrosis than in control lungs, while the vascular density gradually decreased as the degree of fibrosis increased and was lower than that of the control lungs in the most extensively fibrotic lesions. No vessels were observed inside the fibroblastic foci. The potent angiogenic factors, vascular endothelial growth factor and IL-8, were abundantly produced by the capillary endothelial cells and the alveolar epithelial cells in the highly vascularized alveolar walls. In contrast, the venules with CD34-negative but vWF-positive endothelial cells localized in the center of the fibrotic lesions were slightly increased and identified as post-capillary venules by three-dimensional reconstructed images. These results indicate the presence of heterogeneous vascular remodeling in usual interstitial pneumonia.
Key words: idiopathic pulmonary fibrosis, alveolar capillary, endothelial cells




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