Erythrocyte complement receptor type 1 and interactions between immune complexes, neutrophils, and endothelium.
The deposition of immune complexes (IC) may play an important part in the pathogenesis of vasculitis. An increase in permeability of the vascular endothelial lining is a prerequisite for IC deposition. We used an in vitro model to examine the effects of interactions between IC, neutrophils, and endothelium on the integrity of endothelial cell monolayers. Human umbilical vein endothelial cells were grown to confluence on an FITC-labeled matrix, and monolayer integrity was assessed by the exclusion of an 125I-anti-FITC Ab. Alteration in endothelial monolayer permeability was associated with increased uptake of 125I-anti-FITC Ab, expressed as a percentage of the maximal uptake of Ab onto the FITC-matrix from which endothelial cells had been stripped. Neither resting nor cytokine-stimulated endothelial cells bound hepatitis B surface Ag (HBsAg/anti-HBsAg) IC. Immune complexes were shown to activate neutrophils to induce a 9.5% increase in the permeability of IL-1 beta-stimulated endothelium. This increase in endothelial permeability was abrogated by the addition of RBC bearing normal complement receptor type 1 (CR1) numbers (3.2%). This protective effect was shown to be related to the binding of IC to erythrocyte CR1 and was reduced by CR1 blockade using polyclonal rabbit anti-CR1 Abs. These observations demonstrate that IC are capable of directly activating neutrophils to induce increases in endothelial permeability, which may facilitate the deposition of circulating IC. The results support the hypothesis that the binding of IC to erythrocyte CR1 may inhibit damaging interactions between IC, neutrophils, and endothelium.
Beynon
H L
HL
Rheumatology Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Davies
K A
KA
Haskard
D O
DO
Walport
M J
MJ
D000936:Antigen-Antibody Complex / Q000378:metabolism*; D002199:Capillary Permeability; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D004912:Erythrocytes / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology*; D011951:Receptors, Complement; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014657:Vasculitis / Q000276:immunology
D000936:Antigen-Antibody Complex; D006514:Hepatitis B Surface Antigens; D016023:Integrins; D007375:Interleukin-1; D011951:Receptors, Complement; C075060:erythrocyte immune adherence receptor; D013755:Tetradecanoylphorbol Acetate