Pericyte activation and interaction with endothelial cells during lung injury

University Of Washington, Seattle WA

Investigators

Abstract

? DESCRIPTION (provided by applicant): Pericytes are perivascular stromal cells that contribute to microvascular stability through regulation of endothelial homeostasis and barrier integrity. More recently, non-pulmonary pericytes have been shown to participate in tissue leukocyte recruitment following tissue inflammation or injury, through expression of ICAM-1 and various chemokines. Additionally, putative pulmonary pericytes express a variety of immune- related transcripts at baseline. The role of pericytes in the response to lung injury and inflammation is unknown. We hypothesize that in response to lung injury, pericytes transcriptionally upregulate cytokine expression and neutrophil adhesion molecules and suppress endothelial support mechanisms, leading to increased permeability via reduced angiopoietin-1. In the proposed study, I will identify pathways that are dysregulated in pericytes in response to injury using the Ribotag method of isolating cell-specific mRNA. I will also assess whether pericyte toll-like receptor 4 (TLR4) is important in initiating vascular permeability and neutrophil adhesion in response to injurious stimuli. I have shown that the Ribotag method enriches for pericyte-specific mRNA approximately 18-fold, allowing for specific transcriptional analysis. I have also shown that pericytes downregulate angiopoietin-1, a key endothelial support factor, in response to injury. Injured pericytes also upregulate expression of various cytokines and adhesion molecules. Identification of novel cellular actors in acute lung injury will provide more points for intervention in lung injury and inflammation.