Authors:
Stavros Garantziotis, Enrique Zudaire, Carol S Trempus, John W Hollingsworth, Dianhua Jiang, Lisa H Lancaster, Elizabeth Richardson, Lisheng Zhuo, Frank Cuttitta, Kevin K Brown, Paul W Noble, Koji Kimata, and David A Schwartz
Summary:
Background - The etiology and pathogenesis of angiogenesis in idiopathic pulmonary fibrosis (IPF) is poorly understood. Inter-alpha-trypsin inhibitor (IaI) is a serum protein that can bind to hyaluronan and may contribute to the angiogenic response to tissue injury.
Hypothesis - IaI promotes hyaluronan-mediated angiogenesis in tissue injury.
Methods - Examination of angiogenesis in IaI-sufficient and deficient mice in the bleomycin model of pulmonary fibrosis and in angiogenesis assays in vivo and in vitro. Examination of IaI and hyaluronan in patients with IPF.
Results - IaI significantly enhanced the angiogenic response to short-fragment hyaluronan in vivo and in vitro. IaI deficiency led to decreased angiogenesis in the matrigel model, and decreased lung angiogenesis after bleomycin exposure in mice. IaI is found in fibroblastic foci in IPF, where it co-localizes with hyaluronan. The co-localization is particularly strong in vascular areas around fibroblastic foci. Serum levels of IaI and hyaluronan were significantly elevated in IPF patients compared to controls. High serum IaI and hyaluronan levels were associated with decreased lung diffusing capacity, but not forced vital capacity.
Conclusions - Our findings indicate that serum IaI interacts with hyaluronan, and promotes angiogenesis in lung injury. IaI appears to contribute to the vascular response to lung injury and may lead to aberrant angiogenesis.
Source:
American Journal of Respiratory & Critical Care Medicine; Vol. 178, No. 9, 939-947 (11/08)