Via CXCL1/CXCR2 adenosine-mediated pulmonary angiogenesis

Abstract

Introduction: Chronic lung disease's feature is pathological angiogenesis, a still little understood process in this and other diseases. Recently adenosine, a signaling molecule, and chemokines have been considered regulators of this process. Though, relationship between these factors has not been investigated. Objective: To determine the role of adenosine in the induction of angiogenesis during pulmonary chronic inflammation. Design: Experimental. Setting: Bioterio, Immunology Research Group, Facultad de Medicina, Universidad Nacional de San Agustin, Arequipa, Peru, and Biomedical Research Institute, Universidad Nacional Autonoma de Mexico. Biologic material: C57BL/6J adenosine deaminase (ADA)-deficient mice. Methods and interventions: By morphometric analysis we determined relationship between adenosine levels in lung and tracheal angiogenesis, and expression to CXCL1 and its receptor by PCR and Elisa assays. Main outcome measures: Lung adenosine levels, tracheal angiogenesis, and expression to CXCL1 and its receptor. Results: We demonstrated a significant increase of angiogenesis related to high doses of adenosine and an important inhibition of the process when we administered replacement ADA. In the ADA-deficient mice CXCL1 levels rose depending on adenosine levels. CXCL1 receptor (CXCR2) in vivo neutralization showed dramatic inhibition of angiogenic activity. Conclusions: Adenosine may play an important role, via CXCL1/CXCR2, in the induction of pulmonary angiogenesis in pulmonary chronic disease.