title: Effect of clotting factors concentrates on lymphocyte and neutrophil function in vitro.
abstract: Immunological abnormalities have been reported in haemophiliacs. Although infections with HIV, hepatitis and other viruses may contribute to these abnormalities, immune defects are detectable also in HIV seronegative haemophiliacs. It is likely that chronic exposure to extraneous proteins in clotting factor concentrates (CFCs) may play a role in immunomodulation, but the underlying mechanisms remain unclear. The results of the present paper show that: a) soluble HLA class I (sHLA-I), soluble Fas-ligand (sFas-L) and transforming growth factor beta 1 (TGF-beta1) are detectable in plasma derived but not in recombinant CFCs; b) the level of sHLA-I and sFas-L is proportional to the grade of CFCs purity whereas TGF-beta1 showed very variable levels; c) soluble molecules detected in CFCs exert immunomodulatory effects in vitro like apoptosis induction in Jurkat cells and inhibition of mixed lymphocyte reaction response, antigen-specific lymphocyte cytotoxic activity and neutrophil chemotaxis.
authors.affiliation: Department of Internal Medicine (DIMI), University of Genova, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Ghio
authors.forename: Paola
authors.initials: P
authors.lastname: Contini
authors.forename: Luciano
authors.initials: L
authors.lastname: Ottonello
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Arduino
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gringeri
authors.forename: Francesco
authors.initials: F
authors.lastname: Indiveri
authors.forename: Franco
authors.initials: F
authors.lastname: Dallegri
authors.forename: Francesco
authors.initials: F
authors.lastname: Puppo
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001779:Blood Coagulation Factors / Q000235:genetics / Q000302:isolation & purification* / Q000627:therapeutic use; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003601:Cytotoxicity Tests, Immunologic; D004340:Drug Contamination; D053222:Fas Ligand Protein; D006680:HLA Antigens / Q000032:analysis* / Q000097:blood / Q000494:pharmacology; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy; D019169:Jurkat Cells / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000187:drug effects* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000097:blood / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000627:therapeutic use; D016897:Respiratory Burst / Q000187:drug effects; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000097:blood / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
chemical_list: D001779:Blood Coagulation Factors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D006680:HLA Antigens; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D009240:N-Formylmethionine Leucyl-Phenylalanine