Neutrophil interaction with inflamed postcapillary venule endothelium alters annexin 1 expression

Am J Pathol. 2001 Feb;158(2):603-15. doi: 10.1016/S0002-9440(10)64002-3.


Annexin 1 (ANX-A1) exerts antimigratory actions in several models of acute and chronic inflammation. This is related to its ability to mimic the effect of endogenous ANX-A1 that is externalized on neutrophil adhesion to the postcapillary endothelium. In the present study we monitored ANX-A1 expression and localization in intravascular and emigrated neutrophils, using a classical model of rat peritonitis. For this purpose, a pair of antibodies raised against the ANX-A1 N-terminus (ie, able to recognize intact ANX-A1) or the whole protein (ie, able to interact with all ANX-A1 isoforms) was used by immunofluorescence and immunocytochemistry analyses. The majority ( approximately 50%) of ANX-A1 on the plasma membrane of intravascular neutrophils was intact. Extravasation into the subendothelial matrix caused loss of this pool of intact protein (to approximately 6%), concomitant with an increase in total amount of the protein; only approximately 25% of the total protein was now recognized by the antibody raised against the N-terminus (ie, it was intact). In the cytoplasm of these cells, ANX-A1 was predominantly associated with large vacuoles, possibly endosomes. In situ hybridization confirmed de novo synthesis of ANX-A1 in the extravasated cells. In conclusion, biochemical pathways leading to the externalization, proteolysis, and synthesis of ANX-A1 are activated during the process of neutrophil extravasation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A1 / genetics
  • Annexin A1 / metabolism*
  • Annexin A1 / pharmacology
  • Carrageenan / administration & dosage
  • Cell Adhesion
  • Cell Movement
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology*
  • Endothelium, Vascular / ultrastructure
  • Gene Expression Regulation / drug effects
  • Immunohistochemistry
  • In Situ Hybridization
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / pathology
  • Male
  • Mesentery / drug effects
  • Mesentery / metabolism
  • Mesentery / pathology
  • Microscopy, Electron
  • Neutrophils / drug effects
  • Neutrophils / pathology*
  • Peritonitis / chemically induced
  • Peritonitis / metabolism
  • Peritonitis / pathology
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley


  • Annexin A1
  • RNA, Messenger
  • Carrageenan