angiogenin and Asthma

Vascular remodelling plays a central role in asthma and chronic obstructive pulmonary disease (COPD). Bradykinin (BK) is a vasoactive proinflammatory peptide mediating acute responses in asthma. We investigated the role of angiogenic factors in relation to BK receptors in asthma and COPD.. Bronchial biopsies from 33 patients with COPD, 24 old (≥50 years) patients with (≥50 years) asthma, 18 old control smokers, 11 old control non-smokers, 15 young (≤40yrs) patients with (≤40 years) asthma and 10 young control non-smokers were immunostained for CD31, vascular endothelial growth factor-A (VEGF-A), angiogenin and BK receptors (B2R and B1R). Fibroblast and endothelial co-localisation of relevant molecules were performed by immunofluorescence. BK-induced VEGF-A and angiogenin release was studied (ELISA) in bronchial fibroblasts from subjects with asthma and COPD.. In bronchial lamina propria of old patients with asthma, CD31 and VEGF-A(+) cell numbers were higher than old control non-smokers (p<0.05). Angiogenin(+), B2R(+) and B1R(+) cell numbers in old patients with asthma were higher than in old control non-smokers, control smokers and patients with COPD (p<0.01). Angiogenin(+) cell numbers were higher in patients with COPD than both old control groups (p<0.05). In all patients with asthma the number of B2R(+) cells was positively related to the numbers of B1R(+) (rs=0.43), angiogenin(+) (rs=0.42) and CD31 cells (rs=0.46) (p<0.01). Angiogenin(+) cell numbers were negatively related to forced expiratory volume in 1 s (rs=-0.415, p=0.008). Double immunofluorescence revealed that CD31 cells of capillary vessels coexpressed B2R and that fibroblasts coexpressed B2R, VEGF-A and angiogenin. BK (10(-6)M) induced significant angiogenin release in fibroblasts from asthma and to a lesser extent in COPD.. Unlike COPD, this study suggests the involvement of BK receptors in bronchial vascular remodelling in asthma.

Topics: Adaptation, Physiological; Adult; Age Factors; Aged; Asthma; Biomarkers; Bronchi; Capillaries; Case-Control Studies; Endothelial Cells; Female; Fibroblasts; Humans; Male; Middle Aged; Platelet Endothelial Cell Adhesion Molecule-1; Pulmonary Disease, Chronic Obstructive; Receptor, Bradykinin B1; Receptor, Bradykinin B2; Ribonuclease, Pancreatic; Smoking; Vascular Endothelial Growth Factor A; Young Adult

T helper 17 (Th17) cells that produce interleukin (IL)-17A and IL-17F have been found to participate in the development of bronchial asthma and bleomycin-induced pulmonary fibrosis. However, whether they play a causative role in the airway remodeling observed in these respiratory diseases remains unclear. Because fibrocytes are involved in tissue repair and fibrosis and are presumably precursors of lung fibroblasts and myofibroblasts, we examined the effects of IL-17A/F on fibrocyte functions. Both IL-17A and IL-17F enhanced fibrocytes' α-smooth muscle actin expression. Priming fibrocytes with IL-17A enhanced their CD40-mediated IL-6 production, whereas IL-17F-priming increased the CD40-mediated mRNA expression of collagen I, vascular endothelial growth factor, and angiogenin. CD4(+) T cells co-cultured with fibrocytes produced IL-17A, which was inhibited by blocking CD40 and CD40 ligand interactions. These findings suggest that cooperative interactions between fibrocytes and Th17 cells play an important role via CD40- and IL-17A/F-mediated signaling for collagen and proangiogenic factor production, which may lead to the extracellular matrix deposition and neovascularization seen in airway remodeling.

Topics: Actins; Asthma; Bleomycin; CD40 Antigens; Cells, Cultured; Coculture Techniques; Collagen; Fibroblasts; Humans; Interleukin-17; Interleukin-6; Lymphocyte Activation; Mesenchymal Stem Cells; Pulmonary Fibrosis; Ribonuclease, Pancreatic; RNA, Messenger; Signal Transduction; Th17 Cells; Vascular Endothelial Growth Factor A

Airway angiogenesis may be an important part of structural remodelling in the pathogenesis of asthma. The development of asthma is frequently preceded by rhinitis.. We sought to determine whether the levels of angiogenesis-related factors are elevated in airways of patients with rhinitis or controlled asthma.. We analysed the induced sputum of 18 rhinitis patients, 16 asthmatic patients, and 15 healthy controls. The concentrations of angiogenin, vascular endothelial growth factor (VEGF), IL-8, fibroblast growth factor (bFGF), and TNF-alpha were measured by cytometric bead arrays.. We found significantly increased angiogenin and VEGF concentrations in the induced sputum supernatant of both rhinitis and asthma patients compared with that of the healthy control group (P< or =0.0005). With the exception of TNF-alpha, there was no difference in the other angiogenic factors; TNF-alpha levels were higher in the rhinitis group than in the control group (P=0.02).. These in vivo results suggest increased airway angiogenesis in patients with rhinitis without asthma as well as in corticosteroid-treated and well-controlled asthma patients.

Topics: Adolescent; Adult; Aged; Angiogenesis Inducing Agents; Asthma; Cell Count; Eosinophils; Female; Fibroblast Growth Factor 2; Humans; Interleukin-8; Lymphocytes; Macrophages; Male; Middle Aged; Neutrophils; Rhinitis; Ribonuclease, Pancreatic; Sputum; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

ANG is a plasma protein with angiogenic and ribonucleolytic activity implicated in tumor growth, heart failure, wound healing, asthma, and the composition of the adult gut microflora. Human mast cells (HuMC) are similarly associated with modulation of vascular permeability, angiogenic processes, wound healing, and asthma. We hypothesized that HuMC express and secrete ANG in response to divergent stimuli. ANG expression was evaluated in the LAD2 HMC, the HMC-1, and CD34+-derived HuMC, following exposure to live Escherichia coli, TLR ligands, or neuropeptides and following FcepsilonRI aggregation. Expression and production of ANG were determined by microarray analysis, qRT-PCR, confocal microscopy, and ELISA. Microarray analysis showed that ANG is up-regulated by LAD2 cells exposed to live E. coli. qRT-PCR analysis revealed that LAD2, HMC-1, and HuMC constitutively expressed ANG mRNA and that it was up-regulated by exposure to E. coli. Activation of HuMC by FcepsilonRI aggregation resulted in release of small amounts of ANG (<100 pg/mL), whereas compound 48/80, NGF, LPS, PGN, and flagellin activated HuMC to secrete >160 pg/mL ANG. These observations demonstrate that HuMC store and secrete ANG to a variety of stimuli and suggest that MC-derived ANG is available in the subsequent inflammatory response.

Topics: Animals; Asthma; Chickens; Escherichia coli; Flow Cytometry; Humans; Inflammation; Mast Cells; Neoplasms; Neovascularization, Physiologic; Oligonucleotide Array Sequence Analysis; Ribonuclease, Pancreatic; Wound Healing

Angiogenesis is a prerequisite for airway remodeling in bronchial asthma. Several factors may play important roles in inflammation and angiogenesis through effects on inflammatory cell infiltration or neovascularization.. (1) To determine the levels of vascular endothelial growth factor (VEGF) and angiogenin in sputum supernatants of asthmatic children during the acute attack and 6 weeks after start of therapy; and (2) to correlate their levels with the degree of asthma severity.. Twenty asthmatic children with acute attack (mean age, 9.6 +/- 3.5 years [+/- SD]) and 12 sex- and age-matched healthy control children were enrolled in the study. Sputum supernatants were collected for determination of VEGF and angiogenin levels. Serum samples were withdrawn for IgE measurement. The above tests were performed using an enzyme-linked immunosorbent assay. The FEV1 was measured using spirometry. VEGF, angiogenin, and FEV1 estimations were repeated for asthmatic children 6 weeks after start of therapy.. During the acute attack, asthmatic children had significantly higher levels of VEGF and angiogenin than in healthy control children (p < 0.001). VEGF and angiogenin levels showed more elevation with increase in asthma severity (p < 0.001). A significant positive correlation existed between both angiogenic factors (r = 0.98, p < 0.001). A negative significant correlation was found between FEV1 percentage of predicted and both VEGF (r = -0.99, p < 0.001) and angiogenin (r = -0.97, p < 0.001). A nonsignificant correlation was found between serum IgE and sputum VEGF (r = 0.09, p > 0.05). Although there was a significant decrease in the levels of both VEGF and angiogenin after 6 weeks of treatment with corticosteroid inhalation therapy, the levels did not reach normal control levels (p < 0.001 and p < 0.05, respectively).. Our results show that both VEGF and angiogenin levels were elevated in children with acute asthma. The study also suggests that increased severity of bronchial asthma in children is associated with the expression of both angiogenic factors, which are implicated in asthma pathogenesis. After 6 weeks of therapy, the levels of both angiogenic factors showed significant decrease.

Topics: Acute Disease; Adolescent; Angiogenesis Inducing Agents; Asthma; Child; Child, Preschool; Female; Forced Expiratory Volume; Humans; Immunoglobulin E; Male; Ribonuclease, Pancreatic; Sputum; Vascular Endothelial Growth Factor A

We revealed a new property of angiogenin to restore the crystal structure of biological fluids (human blood plasma and exudates) impaired in various pathologies.

Topics: Adolescent; Animals; Anisotropy; Asthma; Blood Proteins; Child; Child, Preschool; Crystallography, X-Ray; Exudates and Transudates; Humans; Milk; Ribonuclease, Pancreatic; Severity of Illness Index

Angiogenesis is a prerequisite for airway remodeling in bronchial asthma. Several growth factors may play important roles in inflammation and angiogenesis through effects on inflammatory cell infiltration or neovascularization.. We sought to compare bronchial vascularity and expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and angiogenin in bronchial biopsy specimens from asthmatic and healthy control subjects.. Bronchial biopsy specimens were obtained from 16 asthmatic subjects and 9 normal control subjects. The number of vessel profiles and the vascular area per unit area on a histologic section were estimated by using computerized image analysis after staining for type IV collagen in vessel walls. Numbers of VEGF+, bFGF+, and angiogenin+ cells were determined by means of immunoreactivity.. The airways of asthmatic subjects had significantly more vessels (P < .05) and greater vascular area (P < .001) than that observed in control subjects. Asthmatic subjects exhibited higher VEGF and bFGF and angiogenin immunoreactivity in the submucosa than did control subjects (P < .001, respectively). Significant correlations were detected between the vascular area and the numbers of angiogenic factor-positive cells (VEGF: rs = 0.93, P < .001; bFGF: rs = 0.83, P < .001; angiogenin: rs = 0.88, P < .001) within the asthmatic airways. Furthermore, the degree of vascularity was inversely correlated with airway caliber and airway responsiveness. Colocalization analysis revealed that the angiogenic factor-positive cells were CD34+ cells, eosinophils, and macrophages.. Our results suggest that increased vascularity of the bronchial mucosa in asthmatic subjects is closely related to the expression of angiogenic factors, which may then contribute to the pathogenesis of asthma.

Topics: Adolescent; Adult; Angiogenesis Inducing Agents; Asthma; Blood Vessels; Endothelial Growth Factors; Fibroblast Growth Factor 2; Humans; Lymphokines; Male; Middle Aged; Neovascularization, Physiologic; Phenotype; Ribonuclease, Pancreatic; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors