Immunoglobulin A: interaction with complement, phagocytic cells and endothelial cells.
Deposits of IgA together with complement (C) in different organs support the hypothesis that IgA can trigger inflammatory mechanisms. Some inflammatory mechanisms may be caused by activation of C and phagocytic cells. Therefore, it is essential to understand the interaction of IgA with C and phagocytic cells. Studies will be described demonstrating that polymeric human serum IgA is able to activate the alternative pathway of C and that the activating principle is located in the intact F(ab')2 portion of the molecule. Activation of C is dependent on the molecular composition of IgA, as derived from results obtained with rat monoclonal IgA antibodies. Furthermore, it is demonstrated that polymeric IgA (pIgA) and dimeric IgA (dIgA) are potent activators of C in a homologous rat model, whereas monomeric IgA (mIgA) has a very poor C-activating potential. The interaction of IgA with phagocytic cells induces phagocytosis and release of H2O2 by granulocytes, which may contribute to tissue damage. Little is known about the clearance mechanism of IgA. It is shown in this report that Kupffer cells and C play an important role in the clearance of IgA immune complexes (IC). Clearance of large-sized IgA IC occurs via different receptors present on Kupffer cells. Finally, a new aspect will be described: the interaction of IgA with endothelial cells. Rat liver endothelial cells are able to eliminate IgA IC from the circulation via specific receptors when no Kupffer cells are present. These observations may contribute to our knowledge on diseases such as IgA nephropathy and Henoch-Schönlein purpura. The studies summarized and presented here illustrate the inflammatory potential of IgA.
Bogers
W M
WM
Department of Nephrology, University Hospital, Leiden, The Netherlands.
Stad
R K
RK
van Es
L A
LA
Daha
M R
MR
D000818:Animals; D003167:Complement Activation / Q000276:immunology*; D003170:Complement Pathway, Alternative / Q000502:physiology; D003165:Complement System Proteins / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D007728:Kupffer Cells / Q000276:immunology*; D010586:Phagocytes / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D051381:Rats
D007070:Immunoglobulin A; D003165:Complement System Proteins