Vasculitis of small blood vessels--some riddles about IgA and about the complexity of transmigration.
Research on leukocytoclastic vasculitis (LcV) provides insights into mechanisms of antibody-mediated immune responses as well as into the complex process of neutrophil transmigration. Clinical observations on immune complex vasculitis have revealed that adult patients with IgA containing immune complexes [Henoch-Schoenlein purpura (HSP)] have a higher rate of severe complications than children with HSP or adult patients with IgG or IgM containing immune complexes. This has direct impact on classification and management of vasculitis and warrants further studies on pathophysiology of IgA and on aberrant glycosylation of IgA1 associated with renal involvement. In order to dissect the pathomechanisms specific for LcV, we have been comparing different mouse models of LcV with a non-vasculitic, acute inflammation (i.e. irritant contact dermatitis). We found that one characteristic constellation in the vasculitis models encompasses interference with both normal transmigration and activation of neutrophils. Toxic products released by activated neutrophils have the potential to damage endothelial cells. However, one still needs to reveal how exactly they exert such damaging effects during diapedesis in vivo, considering the short contacts between neutrophils and endothelial cells. This review shows that research on LcV is embedded in an exciting context revealing special features of transmigration and antibody-mediated immune responses.
Sunderkötter
Cord
C
Department of Dermatology and Institute of Immunology, University of Muenster, Muenster, Germany. Cord.Sunderkoetter@ukmuenster.de
D000818:Animals; D000936:Antigen-Antibody Complex; D001808:Blood Vessels / Q000276:immunology; D002465:Cell Movement; D006031:Glycosylation; D011695:IgA Vasculitis / Q000378:metabolism; D007107:Immune System; D007070:Immunoglobulin A / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009504:Neutrophils / Q000378:metabolism; D014657:Vasculitis / Q000378:metabolism*
D000936:Antigen-Antibody Complex; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M