Complement activation on immunoglobulin G-coated hydrophobic surfaces enhances the release of oxygen radicals from neutrophils through an actin-dependent mechanism

Abstract

Neutrophil granulocytes are among the first cells to encounter a plasma protein-coated implant and may through frustrated phagocytosis release toxic oxidative species. We used two model surfaces, hydrophobic and hydrophilic glass, to investigate the effects of plasma immunoglobulin G (IgG)-complement interactions for neutrophil adhesion and respiratory burst. The respiratory burst was measured with luminol-amplified chemiluminescence and cell adhesion was determined by labeling neutrophils with 2', 7'-bis-(carboxy-ethyl)-5(6)-carboxyfluorescein. We demonstrate that the IgG-triggered neutrophil adhesion and oxygen radical production is augmented in the presence of normal human serum, in particular on hydrophobic surfaces, indicating that complement factors enhance the neutrophil activation. We propose that the complement factors C3, C5a, and C1q are especially important for this amplification, but factor B is probably not. Disturbance of the actin filament dynamics with cytochalasin B or jasplakinolide blocked the neutrophil radical generation on all surfaces. However, these drugs did not affect the number of adherent neutrophils. We suggest that there is a synergistic interaction between adsorbed IgG, and the complement system, which amplifies the neutrophil acute inflammatory responses through a dynamic actin cytoskeleton on synthetic surfaces.

The Initial Inflammatory Response to Bioactive Implants Is Characterized by NETosis

“…In our studies, histone citrullination characteristics support the notion that the vast majority of PMNs attached to SLA titanium surface undergoes NETosis. A main trigger of the inflammatory response to smooth artificial surfaces is the adsorbed IgG [ 9 , 37 , 38 ]. Pre-coating the artificial surfaces with albumin or fibrinogen disables the adhesion of other proteins including IgG and essentially attenuates both PMN adhesion and inflammatory response on smooth artificial surfaces [ 37 – 40 ].…”

Adhesion of human leukocytes on mixtures of hydroxyl‐ and methyl‐terminated self‐assembled monolayers: Effect of blood protein adsorption

“…Other blood plasma proteins also play an important role in host response to implanted medical devices. For example, as described above, C3b adsorbs to the surface of biomaterials, thus activating the complement system which plays a crucial role in the initial reactions against foreign surfaces,24, 31 and immobilized IgG activates the complement system and promotes the adhesion of leukocytes to the surface of biomaterials 22, 32…”

Lack of C3 Affects Th2 Response Development and the Sequelae of Chemotherapy in Schistosomiasis

“…Recent evidence indicates that C3 can play a role in the recruitment of granulocytes during inflammation (29,51,52), as neutrophil infiltration is markedly reduced in C3-deficient mice. In addition, C3 is involved in the IgG-dependent and -independent induction of the respiratory burst in neutrophils (53)(54)(55)(56). Furthermore, complement facilitates killing of the parasitic protozoan Trichomonas vaginalis by neutrophils by enhancing the respiratory burst (53).…”