Opsonic fibronectin is necessary for optimal serum-mediated phagocytosis of Staphylococcus aureus by human neutrophils.
Opsonic fibronectin is known to mediate reticuloendothelial (RE) cell and neutrophil uptake of nonbacterial particulates. In a recent study opsonic fibronectin deficiency following burn preceded the onset of sepsis, leading us to hypothesize a role for this protein in antibacterial defense. To test this hypothesis we compared pooled normal human serum to fibronectin-depleted serum in its ability to opsonize and promote phagocytosis of Staphylococcus aureus by human neutrophil monolayers. Phagocytosis and intracellular killing were evaluated using acridine orange staining and ultraviolet (UV) microscopy. Human serum depleted of opsonic fibronectin by gelatin-sepharose affinity chromatography manifested a marked reduction in its ability to support phagocytosis of S aureus by human neutrophils. Reconstitution of fibronectin-deficient human serum with purified human plasma fibronectin restored its opsonic activity. The direct interaction of fibronectin with the bacteria was shown by mixing and/or incubation of the bacteria with normal serum followed by centrifugation and removal of the bacteria. This resulted in a marked (P less than 0.05) depletion (adsorption) of the fibronectin from the serum. Fibronectin appears not to act independently, but was an important cofactor in the ability for serum to stimulate phagocytosis. Thus, plasma fibronectin may be an important protein essential for maximal opsonic activity of serum. Its depletion following trauma and burn may undermine RE cell and neutrophil defense against infection and bacteremia, thus contributing to organ failure during septic shock.
D005353:Fibronectins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009504:Neutrophils / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects; D012772:Shock, Septic / Q000503:physiopathology; D013211:Staphylococcus aureus / Q000378:metabolism
D005353:Fibronectins