{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T11:51:47Z","timestamp":1790250707455,"version":"4.1.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2012,4,13]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Intravascular neutrophil recruitment and activation are key pathogenic factors that contribute to vascular injury. Intravenous immunoglobulin (IVIG) has been shown to have a beneficial effect in systemic inflammatory disorders; however, the mechanisms underlying IVIG's inhibitory effect on neutrophil recruitment and activation are not understood.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>We studied the mechanisms by which IVIG exerts protection from neutrophil-mediated acute vascular injury.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>We examined neutrophil behavior in response to IVIG in vivo, using real-time intravital microscopy. We found that an antibody that blocks both Fc\u03b3RIII and its inhibitory receptor counterpart, Fc\u03b3RIIB, abrogated the inhibitory effect of IVIG on leukocyte recruitment and heterotypic red blood cell (RBC) interactions with adherent leukocytes in wild-type mice. In the context of sickle cell disease, the blockade of both Fc\u03b3RIIB and III abrogated the protective effect of IVIG on acute vaso-occlusive crisis caused by neutrophil recruitment and activation. Analysis of Fc\u03b3RIIB- and Fc\u03b3RIII-deficient mice revealed the predominant expression of Fc\u03b3RIII on circulating neutrophils. Fc\u03b3RIII mediated IVIG-triggered inhibition of leukocyte recruitment, circulating RBC capture, and enhanced Mac-1 activity, whereas Fc\u03b3RIIB was dispensable. In addition, Fc\u03b3RIII-induced IVIG anti-inflammatory activity in neutrophils was mediated by recruitment of Src homology 2 (SH2)-containing tyrosine phosphatase-1 (SHP-1). Indeed, the protective effect of IVIG on leukocyte recruitment and activation was abrogated in SHP-1-mutant mice.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Fc\u03b3RIII, a classic activating receptor, has an unexpected inhibitory role on neutrophil adhesion and activation via recruitment of SHP-1 in response to IVIG. Our results identify SHP-1 as a therapeutic target in neutrophil-mediated vascular injury.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.112.266411","type":"journal-article","created":{"date-parts":[[2012,3,14]],"date-time":"2012-03-14T04:44:48Z","timestamp":1331700288000},"page":"1057-1066","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":43,"title":["Intravenous Immunoglobulins Modulate Neutrophil Activation and Vascular Injury Through Fc\u03b3RIII and SHP-1"],"prefix":"10.1161","volume":"110","author":[{"given":"Jung-Eun","family":"Jang","sequence":"first","affiliation":[{"name":"From the Department of Medicine, Mount Sinai School of Medicine, New York, NY, and the Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, New York, NY (J.-E.J., P.S.F.); and the Department of Epidemiology, Atherothrombosis, and Imaging, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (A.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"Hidalgo","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Mount Sinai School of Medicine, New York, NY, and the Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, New York, NY (J.-E.J., P.S.F.); and the Department of Epidemiology, Atherothrombosis, and Imaging, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (A.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul S.","family":"Frenette","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Mount Sinai School of Medicine, New York, NY, and the Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, New York, NY (J.-E.J., P.S.F.); and the Department of Epidemiology, Atherothrombosis, and Imaging, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (A.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.66.3.411"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.79.3.549"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth1018"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.052522799"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(92)90796-X"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45336"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.26.021607.090232"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1586\/eci.10.9"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-04-084061"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.105.546150"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-07-2209"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/00024382-199904000-00011"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2206"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00150-9"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.04.013"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.17.10556"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1407"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20072660"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5339.876"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/379346a0"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80494-X"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1939"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.291.5503.484"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.11.010"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1416"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1097\/00062752-200203000-00003"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00080-3"},{"key":"e_1_3_5_29_2","first-page":"31","article-title":"Identification of FcalphaRI as an inhibitory receptor that controls inflammation: dual role of Fcrgamma ITAM","volume":"22","author":"Pasquier B","year":"2005","unstructured":"Pasquier B, Launay P, Kanamaru Y, Moura IC, Pfirsch S, Ruffie C, Henin D, Benhamou M, Pretolani M, Blank U, Monteiro RC . 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