Angiogenic and Angiostatic Chemokines in Idiopathic Pulmonary Fibrosis and Granulomatous Lung Disease

Abstract

Background: Angiogenesis-angiostasis balance and leukocyte recruitment are influenced by different concentrations of distinct chemokines. Objective: To investigate the relative contribution of angiogenic and angiostatic CXC chemokines to the pathogenesis of idiopathic pulmonary fibrosis (IPF) and granulomatous lung diseases, we examined the in vitro production of an angiogenic chemokine (IL-8), and 2 angiostatic chemokines (IP-10 and MIG) by alveolar macrophages. Methods: Alveolar macrophages from 16 patients with granulomatous lung diseases [8 with sarcoidosis, 8 with extrinsic allergic alveolitis (EAA)], 16 patients with IPF, and 8 control subjects were cultured for 24 h. IL-8, IL-18, IP-10 and MIG in the culture supernatants were measured by a fluorescent bead-based multiplex technique. Results: In IPF patients, IL-8 was increased and correlated with bronchoalveolar lavage (BAL) neutrophils, whereas the levels of IP-10 and MIG were normal. In sarcoidosis and EAA patients, IL-8, IP-10, and MIG were all increased and IP-10 and MIG correlated with IL-18, a Th1 cytokine, and the percentage and number of BAL lymphocytes. Conclusions: The difference in the expression of CXC chemokines and a Th1 cytokine may contribute to the different immunopathogenesis, clinical course and responsiveness to treatment of these diseases.

The epithelium in idiopathic pulmonary fibrosis: breaking the barrier

“…Angiogenesis occurs as part of the wound healing process and it has been described around the fibroblastic foci in both IPF patients and in the bleomycin model (Cui et al, 2001; Sterclova et al, 2009). CXC chemokines are important factors in the angiogenic–angiostatic balance as well as being powerful chemoattractants for inflammatory cells (Gerard and Rollins, 2001).…”

Evaluation of chemokines CXCL8 and CCL2, serotonin, and vascular endothelial growth factor serum concentrations in healthy dogs from seven breeds with variable predisposition for canine idiopathic pulmonary fibrosis

“…Furthermore, several studies suggested an involvement of the chemokine CCL2 in the pathogenesis of IPF, notably through its action on resident pulmonary fibroblast and circulating fibrocytes, promoting the generation of abundant extracellular matrix in the lungs (Gharaee-Kermani et al, 1996;Phillips et al, 2004;Moore et al, 2005;Inomata et al, 2014). Such strong evidence involving CXCL8 in the pathogenesis of the disease are lacking, although this chemokine is thought to act as a pro-fibrotic factor in IPF via the promotion of exacerbated angiogenesis (Strieter et al, 2002;Rosenkilde and Schwartz, 2004;Antoniou et al, 2006;Martina et al, 2009;Cui et al, 2010). In dogs, mRNA expression of CXCL8 and CCL2 was found to be increased in CIPF lungs compared with controls .…”

“…Therefore, the aim of the present study was to compare basal circulating blood concentrations of four molecules of interest obtained in healthy dogs from seven breeds differently predisposed to CIPF. Selection of molecules studied was based on their potential implication into the pathogenesis of canine pulmonary fibrosis in view of data from either human or canine literature and were as follows: the chemokine (C-X-C motif) ligand 8 (CXCL8) (Cui et al, 2010;Ahn et al, 2011;Krafft et al, 2013), the chemokine (C-C motif) ligand 2 (CCL2) Moore, 2014), the serotonin (5-HT) (Konigshoff et al, 2010;Krafft et al, 2013), and the vascular endothelial growth factor (VEGF) (Ando et al, 2010;Woodcock et al, 2013).…”

Chemokine receptor CXCR3 ligands in bronchoalveolar lavage fluid: associations with radiological pattern, clinical course, and prognosis in sarcoidosis

“…4,7,15 Many investigators confirmed the importance of the CXCR3-CXCR3 ligand axis in the mobilization of Th1 lymphocytes to the loci of inflammation. 16 The most extensively studied molecule is CXCL10. Agostini et al 7 showed that cells bearing CXCL10 were mainly epithelioid cells and CD68 + macrophages located inside the granulomatous areas.…”