Details

Autor(en) / Beteiligte

• Solowiej, Anna

Titel

Absence of PECAM-1 attenuates foreign -body inflammation due to decreased angiogenesis in and around the implant

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

2002

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• PECAM-1 (platelet endothelial cell adhesion molecule or CD31) is a 130kDa member of the Ig superfamily of proteins and is expressed on endothelial cells, platelets and most leukocytes. It has been implicated as a modulator of angiogenesis, leukocyte transmigration, vascular permeability and β-catenin cycling within endothelial cells. The viability of PECAM-1 knockout (KO) mouse has demonstrated the redundancy of its function during development and during acute inflammatory models. We decided to investigate its function during a chronic process of foreign-body inflammation. Foreign-body inflammation is a reaction to a sterile, inert object. Clinically, it is observed around prosthetic implants and catheter cuffs. It is a mild and a non-specific type of inflammation, yet if it progresses into a chronic phase, it can result in fibrosis and/or hemorrhage due to neovascularization around the implant. We elicited an inflammatory reaction to subcutaneously implanted polyvinyl acetyl sponges in the wild type (WT) and PECAM-1 knockout mice. We observed that on day 7 post-implantation, the KO mice exhibit lower infiltration of neutrophils in and around the implant when compared to the WT animals. In i order to dissect the cell type responsible for this phenotype, we carried out bone marrow transplantations between WT and KO animals. We found that the absence of PECAM-1 on the endothelium (not on the neutrophils) correlates with decreased inflammation, as manifested by lower neutrophil infiltration. We found that PECAM-1-negative animals show decreased angiogenesis inside the implant, resulting in lower blood cell delivery. We investigated the contribution of other endothelial functions to the observed differences. We found that PECAM-1 expression on the neutrophils is important for their transmigration across endothelial monolayers, which may aid in their accumulation in the WT implant (although to a lesser extent than the increased angiogenesis). On the other hand, we found that the differences in vascular permeability between WT and KO animals do not contribute to the observed disparities in neutrophil infiltration. Our study implicates PECAM-1 as a modulator of a clinically-relevant process of foreign-body inflammation. It also shows that CD31 functions in the promotion of angiogenesis, a process central to many physiologic and pathologic conditions.