Inhibition of cell adhesion by antibodies to Arg-Gly-Asp (RGD) in normal immunoglobulin for therapeutic use (intravenous immunoglobulin, IVIg).
Intravenous immunoglobulin (IVIg) therapy is associated with a broad range of immunomodulatory activities. Several of the postulated mechanisms of IVIg action relate to the presence of antibodies to molecules relevant for regulation of the immune response. This article reports that IVIg contains antibodies to the Arg-Gly-Asp (RGD) sequence, and the attachment site of a number of adhesive extracellular matrix proteins, including ligands for beta1, beta3, and beta5 integrins. Anti-RGD antibodies were identified in IVIg by enzyme-linked immunosorbent assay and by using the BIAcore (BIAcore, Uppsala, Sweden) technology. The affinity of anti-RGD antibodies to a synthetic RGD-containing peptide and to fibronectin (Fn) was found to be in the micromolar range. F(ab')2 fragments specific for RGD were purified from IVIg by affinity chromatography. Anti-RGD F(ab')2 antibodies inhibited adenosine diphosphate induced alphaIIb/beta3 integrin-mediated platelet aggregation and the adhesion of activated alpha4beta1 integrin-expressing B cells to Fn. Adhesion of unstimulated platelets to fibrinogen (Fg) involving both the gamma-chain dodecapeptide sequence and the RGD sequence was inhibited by anti-RGD antibodies. In addition, adhesion of thrombin-stimulated platelets to von Willebrand factor or Fg was completely inhibited by affinity-purified anti-RGD antibodies. Our results suggest that the presence of natural IgG antibodies to the RGD motif may contribute to the immunomodulatory and anti-inflammatory effects of therapeutic preparations of normal IgG.
Vassilev
T L
TL
INSERM U430 and the Université Pierre et Marie Curie, Hôpital Broussais, Paris, France.
Kazatchkine
M D
MD
Duong Van Huyen
J P
JP
Mekrache
M
M
Bonnin
E
E
Mani
J C
JC
Lecroubier
C
C
Korinth
D
D
Baruch
D
D
Schriever
F
F
Kaveri
S V
SV
D000906:Antibodies / Q000276:immunology / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D005353:Fibronectins; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology* / Q000627:therapeutic use; D009842:Oligopeptides / Q000276:immunology*; D010973:Platelet Adhesiveness / Q000187:drug effects* / Q000276:immunology; D010974:Platelet Aggregation / Q000187:drug effects* / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology
D000906:Antibodies; D005353:Fibronectins; D016756:Immunoglobulins, Intravenous; D009842:Oligopeptides; D011971:Receptors, Immunologic; C047981:arginyl-glycyl-aspartic acid