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Blood, 15 January 2008, Vol. 111, No. 2, pp. 915-923. Prepublished online as a Blood First Edition Paper on October 11, 2007; DOI 10.1182/blood-2007-04-084061. This Article Full Text (PDF) All Versions of this Article: blood-2007-04-084061v1 111/2/915    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chang, J. Articles by Frenette, P. S Search for Related Content PubMed PubMed Citation Articles by Chang, J. Articles by Frenette, P. S Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 6, 2007 Accepted September 25, 2007 Intravenous immunoglobulins reverse acute vaso-occlusive crises in sickle cell mice through rapid inhibition of neutrophil adhesion Jungshan Chang, Patricia A. Shi, Elaine Y Chiang, and Paul S Frenette* Department of Medicine, Immunobiology Center and Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, NY, United States * Corresponding author; email: paul.frenette{at}mssm.edu. Previous studies using intravital microscopy in a sickle cell disease (SCD) mouse model suggest that adherent leukocytes (WBCs) play a key role in vaso-occlusion by capturing circulating erythrocytes (RBCs) in venules. Commercial intravenous human gamma globulins (IVIG) given prior to the inflammatory stimuli increase microcirculatory blood flow and improved survival. To mimic the clinical situation where SCD patients seek medical attention after the onset of symptoms, we have developed an in vivo model in which the therapeutic intervention (e.g. IVIG) was administered after in the inflammatory challenge. In this setting, IVIG rapidly (<10 min) reduced adherent leukocyte numbers and dramatically inhibited the interactions between RBCs and WBCs, resulting in improved microcirculatory blood flow and survival of sickle cell mice. Longer survival correlated positively with blood flow (p=0.001) and negatively with the number of adherent leukocytes (p=0.001) and RBC-WBC interactions (p=0.0002). Using multichannel digital fluorescence videomicroscopy, we found that IVIG affected specifically the recruitment of neutrophils. Moreover, further analyses of leukocyte behavior revealed that IVIG significantly increased rolling velocities, indicating that it alters adhesion pathways involved in slow rolling. These data suggest that the potential therapeutic benefits of IVIG in SCD crises should be evaluated in a clinical trial. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. D. Wagner and P. S. Frenette The vessel wall and its interactions Blood, June 1, 2008; 111(11): 5271 - 5281. [Abstract] [Full Text] [PDF]

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