{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T01:59:06Z","timestamp":1782179946464,"version":"3.54.5"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T00:00:00Z","timestamp":1646352000000},"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>The phagocytosis-promoting complement receptor, Complement Receptor Immunoglobulin (CRIg), is exclusively expressed on macrophages. It has been demonstrated that expression in macrophages could be modulated by inflammatory mediators, including cytokines. This raised the possibility that a major phagocyte, the neutrophil, may also express CRIg following activation with inflammatory mediators. Here we show that resting peripheral blood neutrophil lysates subjected to protein analysis by Western blot revealed a 35 kDa CRIg isoform, consistent with the expression of CRIg mRNA by RT-PCR. By flow cytometry, CRIg was detected intracellularly and in very minor amounts on the cell surface. Interestingly, expression on the cell surface was significantly increased to functional levels after activation with inflammatory mediators\/neutrophil activators; N-Formylmethionine-leucyl-phenylalanine, tumor necrosis factor (TNF), Granulocyte-Macrophage Colony stimulating Factor (GM-CSF), bacterial lipopolysaccharide, leukotriene B4 and phorbol myristate acetate. The increase in expression required p38 MAP kinase and protein kinase C activation, as well as intracellular calcium. Neutrophils which were defective in actin microfilament reorganization due to a mutation in ARPC1B or inhibition of its upstream regulator, Rac2 lose their ability to upregulate CRIg expression. Inhibition of another small GTPase, Rab27a, with pharmacological inhibitors prevented the increase in CRIg expression, suggesting a requirement for the actin cytoskeleton and exocytosis. Engagement of CRIg on TNF-primed neutrophils with an anti-CRIg monoclonal antibody increased the release of superoxide and promoted the activation of p38 but not ERK1\/ERK2 or JNK MAP kinases. The TNF-induced increase in killing of<jats:italic>Staphylococcus aureus<\/jats:italic>was blocked by the anti-CRIg antibody. Adding to the anti-microbial role of CRIg, it was found that GM-CSF priming lead to the release of neutrophil extracellular traps. Interestingly in contrast to the above mediators the anti-inflammatory cytokine IL-10 caused a decrease in basal expression and GM-CSF induced increase in CRIg expression. The data demonstrate that neutrophils also express CRIg which is regulated by inflammatory mediators and cytokines. The findings show that the neutrophil antimicrobial function involving CRIg requires priming as a means of arming the cell strategically with microbial invasion of tissues and the bloodstream.<\/jats:p>","DOI":"10.3389\/fimmu.2022.840510","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T07:25:22Z","timestamp":1646378722000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Neutrophils Require Activation to Express Functional Cell-Surface Complement Receptor Immunoglobulin"],"prefix":"10.3389","volume":"13","author":[{"given":"Annabelle G.","family":"Small","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalida","family":"Perveen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trishni","family":"Putty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Quinn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihir D.","family":"Wechalekar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles S.","family":"Hii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Quach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Ferrante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.12.039","article-title":"Crig: A Macrophage Complement Receptor Required for Phagocytosis of Circulating Pathogens","volume":"124","author":"Helmy","year":"2006","journal-title":"Cell"},{"key":"B2","doi-asserted-by":"publisher","first-page":"w14301","DOI":"10.4414\/smw.2016.14301","article-title":"Complement Receptor Immunoglobulin: A Control Point in Infection and Immunity, Inflammation and Cancer","volume":"146","author":"Small","year":"2016","journal-title":"Swiss Med Wkly"},{"key":"B3","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.chom.2016.05.023","article-title":"Dual-Track Clearance of Circulating Bacteria Balances Rapid Restoration of Blood Sterility With Induction of Adaptive Immunity","volume":"20","author":"Broadley","year":"2016","journal-title":"Cell Host Microbe"},{"key":"B4","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.chom.2016.06.002","article-title":"Crig Functions as a Macrophage Pattern Recognition Receptor to Directly Bind and Capture Blood-Borne Gram-Positive Bacteria","volume":"20","author":"Zeng","year":"2016","journal-title":"Cell Host Microbe"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25673","article-title":"Vsig4, a B7 Family-Related Protein, Is a Negative Regulator of T Cell Activation","volume":"116","author":"Vogt","year":"2006","journal-title":"J Clin Invest"},{"key":"B6","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1038\/s42003-021-01943-3","article-title":"Vitamin D Upregulates the Macrophage Complement Receptor Immunoglobulin in Innate Immunity to Microbial Pathogens","volume":"4","author":"Small","year":"2021","journal-title":"Commun Biol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201040323","article-title":"Inhibition of the Alternative Pathway of Complement Activation Reduces Inflammation in Experimental Autoimmune Uveoretinitis","volume":"40","author":"Chen","year":"2010","journal-title":"Eur J Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070432","article-title":"A Novel Inhibitor of the Alternative Pathway of Complement Reverses Inflammation and Bone Destruction in Experimental Arthritis","volume":"204","author":"Katschke","year":"2007","journal-title":"J Exp Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260419","article-title":"Proteomics. 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