Mononuclear cells ingest E. coli opsonized by investigational intravenous immunoglobulin preparations in the absence of complement more efficiently than polymorphonuclear phagocytes.
OBJECTIVE
The increasing use of intravenous immunoglobulins (IVIg) to treat systemic inflammatory, mostly autoimmune, diseases raises the concern that their competition for FcgammaReceptor (FcgammaR) binding with immune complexes might interfere with the removal of opsonized microbial agents more than it favoured their opsonophagocytosis.


METHODS
Using a sensitive FACS-based phagocytosis assay allowing for the identification of the phagocytosing cell-type, we have tested the relative capacity of Pentaglobin and two investigational IVIg preparations, IVIgG and IVIgM, to promote E. coli phagocytosis. The plasma IL-8 levels 4 h after phagocytosis were measured by ELISA.


RESULTS
Heat inactivated, complement (C) depleted serum allowed about 25% polymorphonuclear leukocytes (PMNLs) and 15% monocytes (MNs) of 16 donors to phagocyte E. coli. The addition of IVIg favoured mean phagocytosis by MNs to 55%, but by PMNLs only to 25%. The addition of fresh autologous plasma as a C source resulted in a boost of phagocytosing capacity to reach >90% of the PMNLs and >72% of the MNs. Blockade of FcgammaRII and FcgammaRI using monoclonal antibodies (mAb) reduced phagocytosis and IL-8 release.


CONCLUSIONS
We conclude that excess IVIgG/M preparations added to a phagocytic system of PMNLs and MNs, without preopsonization of E. coli, promotes phagocytosis as expected, but MNs rather than PMNLs do this more thoroughly on their own.
Tinguely
C
C
Department of Hematology, Bern University Hospital, Inselspital, Switzerland.
Schaller
M
M
Nydegger
U E
UE
D004926:Escherichia coli / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology*; D016209:Interleukin-8 / Q000097:blood / Q000378:metabolism; D009000:Monocytes / Q000382:microbiology / Q000502:physiology*; D009504:Neutrophils / Q000382:microbiology / Q000502:physiology; D009895:Opsonin Proteins / Q000276:immunology*; D010587:Phagocytosis; D017452:Receptors, IgG / Q000276:immunology
D016756:Immunoglobulins, Intravenous; D016209:Interleukin-8; D009895:Opsonin Proteins; D017452:Receptors, IgG