The Actin Cytoskeleton Responds to Inflammatory Cues and Alters Macrophage Activation

Elsa Ronzier, Alexander J. Laurenson, Rohini Manickam, Sophia Liu, Imelda M. Saintilma, Dillon C. Schrock, John A. Hammer, Jeremy D. Rotty*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Much remains to be learned about the molecular mechanisms underlying a class of human disorders called actinopathies. These genetic disorders are characterized by loss-of-function mutations in actin-associated proteins that affect immune cells, leading to human immunopathology. However, much remains to be learned about how cytoskeletal dysregulation promotes immunological dysfunction. The current study reveals that the macrophage actin cytoskeleton responds to LPS/IFNγ stimulation in a biphasic manner that involves cellular contraction followed by cellular spreading. Myosin II inhibition by blebbistatin blocks the initial contraction phase and lowers iNOS protein levels and nitric oxide secretion. Conversely, conditional deletion of Arp2/3 complex in macrophages attenuates spreading and increases nitric oxide secretion. However, iNOS transcription is not altered by loss of myosin II or Arp2/3 function, suggesting post-transcriptional regulation of iNOS by the cytoskeleton. Consistent with this idea, proteasome inhibition reverses the effects of blebbistatin and rescues iNOS protein levels. Arp2/3-deficient macrophages demonstrate two additional phenotypes: defective MHCII surface localization, and depressed secretion of the T cell chemokine CCL22. These data suggest that interplay between myosin II and Arp2/3 influences macrophage activity, and poten-tially impacts adaptive-innate immune coordination. Disrupting this balance could have detrimental impacts, particularly in the context of Arp2/3-associated actinopathies.

Original languageEnglish
Article number1806
Issue number11
StatePublished - 1 Jun 2022
Externally publishedYes


  • Arp2/3 complex
  • CCL22
  • actin cytoskeleton
  • iNOS
  • inflammation
  • macrophages
  • myosin-II


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