Intravenous immune globulin prevents venular vaso-occlusion in sickle cell mice by inhibiting leukocyte adhesion and the interactions between sickle erythrocytes and adherent leukocytes.
Sickle cell vaso-occlusion is a complex multistep process likely involving heterotypic interactions among sickle erythrocytes (red blood cells [RBCs]), leukocytes (white blood cells [WBCs]), and endothelial cells. Recent data using intravital microscopy in a sickle cell mouse model suggest that adherent leukocytes in postcapillary venules play a critical role in vaso-occlusion by capturing circulating sickle RBCs. In the course of studies to investigate the adhesion receptors mediating sickle RBC-WBC interactions, we found that control nonspecific immunoglobulin G (IgG) preparations displayed significant inhibitory activity. As a result, we studied the effects of commercial intravenous human immune globulin (i.v.IG) preparations and found that i.v.IG inhibits RBC-WBC interactions in cremasteric venules in a dose-dependent manner. i.v.IG of at least 200 mg/kg dramatically reduced these interactions, even after tumor necrosis factor-alpha (TNF-alpha) stimulation, and not only increased microcirculatory blood flow but also improved survival of sickle cell mice. These data raise the possibility that i.v.IG may have a beneficial effect on sickle cell-associated vaso-occlusion.
Turhan
Aslihan
A
Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1079, New York, NY 10029, USA.
Jenab
Pegah
P
Bruhns
Pierre
P
Ravetch
Jeffrey V
JV
Coller
Barry S
BS
Frenette
Paul S
PS
D000755:Anemia, Sickle Cell / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002448:Cell Adhesion / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002470:Cell Survival; D004912:Erythrocytes / Q000166:cytology* / Q000276:immunology; D007074:Immunoglobulin G / Q000378:metabolism / Q000494:pharmacology; D016756:Immunoglobulins, Intravenous; D007962:Leukocytes / Q000166:cytology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000098:blood supply; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014699:Venules / Q000502:physiology
D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D014409:Tumor Necrosis Factor-alpha