NDLI: The Actin Cytoskeleton Responds to Inflammatory Cues and Alters Macrophage Activation

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The Actin Cytoskeleton Responds to Inflammatory Cues and Alters Macrophage Activation

Content Provider	MDPI
Author	Ronzier, Elsa Laurenson, Alexander J. Manickam, Rohini Liu, Sophia Saintilma, Imelda M. Schrock, Dillon C. Hammer, John A. Rotty, Jeremy D.
Copyright Year	2022
Description	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 potentially impacts adaptive-innate immune coordination. Disrupting this balance could have detrimental impacts, particularly in the context of Arp2/3-associated actinopathies.
Starting Page	1806
e-ISSN	20734409
DOI	10.3390/cells11111806
Journal	Cells
Issue Number	11
Volume Number	11
Language	English
Publisher	MDPI
Publisher Date	2022-05-31
Access Restriction	Open
Subject Keyword	Cells Immunology Actin Cytoskeleton Arp2/3 Complex Myosin-ii Macrophages Inos Inflammation Ccl22
Content Type	Text
Resource Type	Article

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