L Wright, RM Tuder, J Wang, CD Cool, RA Lepley and NF Voelkel
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.

Inflammatory infiltrates and endothelial cell proliferation have been appreciated in plexiform and concentric lesions, which characterize the vascular remodeling in primary pulmonary hypertension (PPH). Leukotriene production by perivascular and alveolar macrophages relies on activation of 5-lipoxygenase (5-LO), with translocation of the enzyme to the nuclear membrane, and association with the 5-LO activating protein (FLAP). Using immunohistochemical staining, we localized and semi-quantitatively estimated the abundance of 5-LO and FLAP in lungs obtained from patients with PPH, patients with interstitial lung disease (ILD), and normal control subjects. Expression of 5-LO and FLAP was prominent in alveolar macrophages in both the normal and PPH lungs; however, alveolar macrophages were more frequently clustered in the vicinity of remodeled blood vessel in PPH. Medium- and small-size pulmonary arteries in PPH showed more abundant FLAP expression than in control and ILD lungs. 5-LO expression in small arteries in PPH was more intense than in control and ILD patients. Endothelial cells in plexiform and concentric lesions in PPH expressed both 5-LO and FLAP. In situ hybridization confirmed the presence of 5- LO transcripts in macrophages and endothelial cells of the remodeled vessels in PPH. We propose that the overexpression of 5-LO and FLAP represents evidence for the participation of inflammation in the process of PPH vasculopathy or, alternatively, that the overabundance of the enzymes involved in generation of inflammatory mediators may themselves be related to vascular cell proliferation and cell growth.

This article has been cited by other articles:

				J. L. Walker, J. Loscalzo, and Y.-Y. Zhang 5-Lipoxygenase and human pulmonary artery endothelial cell proliferation Am J Physiol Heart Circ Physiol, February 1, 2002; 282(2): H585 - H593. [Abstract] [Full Text] [PDF]

				H. KIMURA, O. OKADA, N. TANABE, Y. TANAKA, M. TERAI, Y. TAKIGUCHI, M. MASUDA, N. NAKAJIMA, K. HIROSHIMA, H. INADERA, et al. Plasma Monocyte Chemoattractant Protein-1 and Pulmonary Vascular Resistance in Chronic Thromboembolic Pulmonary Hypertension Am. J. Respir. Crit. Care Med., July 15, 2001; 164(2): 319 - 324. [Abstract] [Full Text] [PDF]

				S.-J. Chu, L.-O. Tang, E. Watney, E. Y. Chi, and W. R. Henderson Jr. In Situ Amplification of 5-Lipoxygenase and 5-Lipoxygenase-Activating Protein in Allergic Airway Inflammation and Inhibition by Leukotriene Blockade J. Immunol., October 15, 2000; 165(8): 4640 - 4648. [Abstract] [Full Text] [PDF]

				M. PETERS-GOLDEN and T. G. BROCK Intracellular Compartmentalization of Leukotriene Biosynthesis Am. J. Respir. Crit. Care Med., February 1, 2000; 161(2): S36 - 40. [Full Text] [PDF]

				C. D. Cool, J. S. Stewart, P. Werahera, G. J. Miller, R. L. Williams, N. F. Voelkel, and R. M. Tuder Three-Dimensional Reconstruction of Pulmonary Arteries in Plexiform Pulmonary Hypertension Using Cell-Specific Markers : Evidence for a Dynamic and Heterogeneous Process of PulmonaryEndothelial Cell Growth Am. J. Pathol., August 1, 1999; 155(2): 411 - 419. [Abstract] [Full Text] [PDF]

				R. M. TUDER, C. D. COOL, M. W. GERACI, J. WANG, S. H. ABMAN, L. WRIGHT, D. BADESCH, and N. F. VOELKEL Prostacyclin Synthase Expression Is Decreased in Lungs from Patients with Severe Pulmonary Hypertension Am. J. Respir. Crit. Care Med., June 1, 1999; 159(6): 1925 - 1932. [Abstract] [Full Text]