title: A component of factor VIII preparations which can be separated from factor VIII activity down modulates human monocyte functions.
abstract: In this study we investigated different aspects of monocyte functions following interaction of monocytes (Mo) with therapeutic concentrations of factor VIII (F VIII) concentrate. A short (one-hour) treatment of normal Mo with F VIII concentrates led to a significant (P less than 0.001) down modulation of Fc receptors expressed in the Mo plasma membrane. This down modulation was accompanied by a decrease of Mo effector functions that was expressed by a reduced capacity of F VIII-treated Mo to release O2 radicals (40% of controls) and to kill bacteria (% killing: control Mo, 65%; F VIII-treated Mo, 24% to 51%). Further studies showed that the modulating activity was due to a contaminant present in F VIII concentrates (immune complexes or IgG aggregates). Fractionation using molecular sieving revealed that the modulatory activity was confined to a high-molecular range fraction (Mr greater than 1,270,000 daltons), while the fraction containing monomeric IgG had no effect. Further fractionation by affinity chromatography on protein A-Sepharose separated the coagulation activity (effluent) from the Mo function-modulating activity (eluate). We conclude that treatment with F VIII concentrates might contribute to an immunocompromised state in some hemophiliacs and facilitate opportunistic infections in these patients.
mesh_terms: D000936:Antigen-Antibody Complex; D001770:Blood Bactericidal Activity / Q000187:drug effects; D005169:Factor VIII / Q000009:adverse effects / Q000032:analysis* / Q000276:immunology; D006467:Hemophilia A / Q000188:drug therapy; D006801:Humans; D008163:Luminescent Measurements; D046911:Macromolecular Substances; D008970:Molecular Weight; D009000:Monocytes / Q000187:drug effects*; D011961:Receptors, Fc / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D000936:Antigen-Antibody Complex; D046911:Macromolecular Substances; D011961:Receptors, Fc; D013481:Superoxides; D005169:Factor VIII