{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T22:38:09Z","timestamp":1778279889275,"version":"3.51.4"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T00:00:00Z","timestamp":1622419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Neutrophil trafficking, homeostatic and pathogen elicited, depends upon chemoattractant receptors triggering heterotrimeric G-protein G\u03b1\n                    <jats:sub>i<\/jats:sub>\n                    \u03b2\n                    <jats:italic>\u03b3<\/jats:italic>\n                    signaling, whose magnitude and kinetics are governed by RGS protein\/G\u03b1\n                    <jats:sub>i<\/jats:sub>\n                    interactions. RGS proteins typically limit G\u03b1\n                    <jats:sub>i<\/jats:sub>\n                    signaling by reducing the duration that G\u03b1\n                    <jats:sub>i<\/jats:sub>\n                    subunits remain GTP bound and able to activate downstream effectors. Yet how in totality RGS proteins shape neutrophil chemoattractant receptor activated responses remains unclear. Here, we show that C57Bl\/6 mouse neutrophils containing a genomic knock-in of a mutation that disables all RGS protein-G\u03b1\n                    <jats:sub>i2<\/jats:sub>\n                    interactions (G184S) cannot properly balance chemoattractant receptor signaling, nor appropriately respond to inflammatory insults. Mutant neutrophils accumulate in mouse bone marrow, spleen, lung, and liver; despite neutropenia and an intrinsic inability to properly mobilize from the bone marrow.\n                    <jats:italic>In vitro<\/jats:italic>\n                    they rapidly adhere to ICAM-1 coated plates, but\n                    <jats:italic>in vivo<\/jats:italic>\n                    they poorly adhere to blood vessel endothelium. Those few neutrophils that cross blood vessels and enter tissues migrate haphazardly. Following Concanavalin-A administration fragmented G184S neutrophils accumulate in liver sinusoids leading to thrombo-inflammation and perivasculitis. Thus, neutrophil G\u03b1\n                    <jats:sub>i2<\/jats:sub>\n                    \/RGS protein interactions both limit and facilitate G\u03b1\n                    <jats:sub>i2<\/jats:sub>\n                    signaling thereby promoting normal neutrophil trafficking, aging, and clearance.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2021.679856","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T04:38:52Z","timestamp":1622435932000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Unrestrained G\u03b1i2 Signaling Disrupts Neutrophil Trafficking, Aging, and Clearance"],"prefix":"10.3389","volume":"12","author":[{"given":"Serena Li-Sue","family":"Yan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Il-Young","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olena","family":"Kamenyeva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juraj","family":"Kabat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Sung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chung","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John 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