Transgenic mice expressing different levels of soluble PECAM-IgG display distinct inflammatory phenotypes

Fang Liao*, William A. Müller

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

PECAM-1 (CD31), an adhesion molecule on the surfaces of leukocytes and in the junctions between endothelial cells has been demonstrated to play an important rote in transendothelial migration of neutrophils (PMN) and monocytes (Mo). Soluble recombinant PECAM-IgG blocks acute leukocyte emigration into the peritoneal cavity in response to thioglycollate broth. In order to study the function of PECAM in chronic inflammation, transgenic mice expressing soluble murine PECAM-IgG were generated. Three founder lines were identified by genomic Southern analysis. Transgenic protein expression in serum was quantitated by ELISA. Heterozygotes from the three lines displayed quite different PECAM-IgG plasma levels: ∼10 μg/ml (Tg8), ∼100 μg/ml (Tg5), and ∼2 mg/ml (Tg11). All mice were healthy and showed hematologic profiles identical to their wild-type littermates. Leukocyte migration into the peritoneal cavity in response to thioglycollate was significantly reduced in Tg8 mice. Accumulation of PMN and Mo was blocked by 45% and 80%, respectively, in heterozygotes (∼10 μg/ml) and 80% and 100%, respectively, in homozygotes (∼20 μg/ml). In contrast, leukocytes of Tg5 and Tg11 mice showed the same response to thioglycollate as wild-type despite the significantly higher PECAM-IgG levels. The PECAM-IgG in these mice was functional; when administered exogenously to wild-type mice it blocked inflammation. The expression of endogenous PECAM as well as of leukocyte CD11a, CD11b, and CD18 in these mice was indistinguishable from wild-type controls. We are breeding Tg8 mice for studies of the role of PECAM in chronic inflammation. Tg5 and Tg11 mice are currently being studied in other models of inflammation. They may provide insights into the mechanisms of PECAM-independent transmigration.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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