Platelet retention in inflamed glomeruli occurs via selective prolongation of interactions with immune cells

Michaela Finsterbusch, M. Ursula Norman, Pam Hall, A. Richard Kitching, Michael J. Hickey

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

Platelet-leukocyte interactions promote acute glomerulonephritis. However, neither the nature of the interactions between platelets and immune cells nor the capacity of platelets to promote leukocyte activation has been characterized in this condition. We used confocal intravital microscopy to define the interactions of platelets with neutrophils, monocytes, and endothelial cells in glomerular capillaries in mice. In the absence of inflammation, platelets underwent rapid on/off interactions with immune cells. During glomerulonephritis induced by in situ immune complex formation, platelets that interacted with neutrophils or monocytes, but not with other intraglomerular cells, were retained in the glomerulus for prolonged durations. Depletion of platelets inhibited both neutrophil recruitment and activation. Inhibition of platelet activating factor reduced neutrophil recruitment without impacting reactive oxygen species generation, while blocking CXC chemokine ligand 7 (CXCL7) reduced both responses. In contrast, inhibition of the adenosine diphosphate and thromboxane A2 pathways inhibited neutrophil reactive oxygen species generation without affecting neutrophil adhesion. Thus, platelet retention in glomerular capillaries following immune complex deposition stems from prolongation of platelet interactions with immune cells but not other substrates. Pro-inflammatory mediators play divergent roles in promoting neutrophil retention and activation in glomerular capillaries.

Original languageEnglish
Pages (from-to)363-374
Number of pages12
JournalKidney International
Volume95
Issue number2
DOIs
Publication statusPublished - 1 Feb 2019

Keywords

  • glomerulonephritis
  • inflammation
  • oxidative stress
  • platelet

Cite this