title: Imbalance in the expression of CXC chemokines correlates with bronchoalveolar lavage fluid angiogenic activity and procollagen levels in acute respiratory distress syndrome.
abstract: Diffuse alveolar damage is the histopathological hallmark of acute respiratory distress syndrome (ARDS) and is a stereotypic response to a variety of etiologies. Moreover, a significant proportion of ARDS survivors have residual pulmonary fibrosis and compromised pulmonary function. This suggests that the pathogenesis of diffuse alveolar damage that ultimately leads to the chronic fibrosis of ARDS has features of dysregulated repair exemplified by exaggerated intra-alveolar angiogenesis and fibrogenesis (i.e., fibroproliferation and deposition of extracellular matrix), leading to progressive alveolar fibrosis and impaired lung function. We obtained bronchoalveolar lavage fluid (BALF) from patients with ARDS or ventilated control patients and assessed CXC chemokine levels by ELISA. We found an imbalance in the expression of ELR(+) as compared with ELR(-) CXC chemokines from BALF of patients with ARDS as compared with controls. This imbalance correlated with angiogenic activity as assessed by the corneal micropocket assay. Furthermore, these levels correlated with both procollagen I and procollagen III levels in BALF. In contrast, while BALF levels of vascular endothelial growth factor were elevated, vascular endothelial growth factor did not appear to be significantly contributing to the angiogenic activity. These findings suggest that CXC chemokines have an important role in the fibroproliferative phase of ARDS via the regulation of angiogenesis.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California, Los Angeles 90095, USA. mpkeane@mednet.ucla.edu
authors.forename: Michael P
authors.initials: MP
authors.lastname: Keane
authors.forename: Seamas C
authors.initials: SC
authors.lastname: Donnelly
authors.forename: John A
authors.initials: JA
authors.lastname: Belperio
authors.forename: Richard B
authors.initials: RB
authors.lastname: Goodman
authors.forename: Maria
authors.initials: M
authors.lastname: Dy
authors.forename: Marie D
authors.initials: MD
authors.lastname: Burdick
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fishbein
authors.forename: Robert M
authors.initials: RM
authors.lastname: Strieter
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001681:Biological Assay; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology*; D016022:Case-Control Studies; D019743:Chemokines, CXC / Q000737:chemistry / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008168:Lung / Q000276:immunology; D008222:Lymphokines / Q000378:metabolism; D009389:Neovascularization, Pathologic; D011347:Procollagen / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051381:Rats; D012128:Respiratory Distress Syndrome / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D019743:Chemokines, CXC; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D011347:Procollagen; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors