PECAM-Independent Thioglycollate Peritonitis Is Associated With a Locus on Murine Chromosome 2

Abstract

BackgroundPrevious studies have demonstrated that knockout or inhibition of Platelet/Endothelial Cell Adhesion Molecule (PECAM, CD31) in a number of murine strains results in impaired inflammatory responses, but that no such phenotype is seen in the C57BL/6 (B6) murine background.Methodology/Principal FindingsWe have undertaken a quantitative trait locus (QTL) mapping effort between FVB/n (FVB) and B6 mice deficient for PECAM to identify the gene or genes responsible for this unique feature of B6 mice. We have identified a locus on murine chromosome 2 at approximately 35.8 Mb that is strongly associated (LOD score = 9.0) with inflammatory responses in the absence of PECAM.Conclusions/SignificanceThese data potentiate further study of the diapedesis machinery, as well as potential identification of new components of this machinery. As such, this study is an important step to better understanding the processes of inflammation.

4D intravital microscopy uncovers critical strain differences for the roles of PECAM and CD99 in leukocyte diapedesis

“…However, these differences were found not to be significant (P Ͼ 0.13). Although this difference was not statistically significant, this finding is in line with previously published reports that have described the C57BL/6 strain as a hyperinflammatory mouse model (26), which partially explains its popularity in the field of immunology.…”

“…Our in vivo studies reported here were limited to PMN interactions in acute inflammatory settings. Based on previous studies (22,26), we predict that monocytes would behave similarly.…”

“…A previous study from our laboratory used quantitative trait loci (QTL) mapping between C57BL/6 and FVB/n PECAM Ϫ/Ϫ mice to identify a 35.8-Mb locus on murine chromosome 2 associated with PECAM-independent inflammation in the thioglycollate peritonitis model (26). Within this QTL locus were multiple genes, notably COX-1 (Ptgs1) and PGE 2 synthases 1 and 2 (Ptges and Ptges2).…”

“…PECAM blockade in vivo has been shown to inhibit leukocyte transmigration in all mouse strains tested except C57BL/6 mice and to arrest leukocytes along the endothelium in FVB/n mice, replicating findings in human cells in vitro. In contrast, in PECAM-deficient C57BL/6 mice, there is a transient defect in crossing the endothelial basement membrane (5, 9, 38) or no detectable effect on transmigration, depending on the time of observation and the inflammatory model (9,22,26).…”

Imbricaric Acid and Perlatolic Acid: Multi-Targeting Anti-Inflammatory Depsides from Cetrelia monachorum

“…This observed inhibition of leukocyte recruitment compares well with the reported inhibition of recruitment by other inhibitors of the NF-κB- [33] and 5-LO- signaling pathways [34] and with the suggestion that mPGES-1 might be a likely candidate for a role as PCAM-1 independent modulator of leukocyte recruitment [35]. More detailed future analysis of the bioactive depsides in diverse animal models of inflammation e.g.…”