Variability of biological effects of silicas: different degrees of activation of the fifth component of complement by amorphous silicas.
A biogenic and a pyrogenic amorphous silica were incubated in normal human plasma and compared on a per unit surface basis for their ability to split C5 molecules and yield small C5a peptides. Since C5a peptides induce selective chemotactic attraction of polymorphonuclear leukocytes (PMN), measurement of PMN-induced chemotaxis was used as an index of C5 activation. Though to a lesser extent than the crystalline forms, amorphous silicas can promote the cleavage of C5 protein and generation of C5a-like fragment. The biogenic silica, which differs from the pyrogenic variety in particle shape, level of contaminants, and degree of surface hydrophilicity, besides specific surface, induced a greater response. Both silicas activated C5 through a process which seems to involve multiple events similar to those induced by crystalline silica. C5 molecules are adsorbed and hydroxyl radicals are generated through Haber Weiss cycles catalyzed by the redox-active iron present at the particle surface either as trace impurities or chelated from plasma by silanol groups. In turn, these radicals convert native C5 to an oxidized C5-like form C5(H2O2). Finally, C5(H2O2) is cleaved by protease enzymatic action of plasma kallikrein activated by the same silica dusts, yielding a product, C5a(H2O2), having the same functional characteristic as C5a.
Governa
Mario
M
Department of Molecular Pathology, Institute of Occupational Medicine, Polytechnic University of Marche, Ancona, Italy.
Amati
Monica
M
Fenoglio
Ivana
I
Valentino
Matteo
M
Coloccini
Sabrina
S
Bolognini
Lucia
L
Carlo Botta
Gian
G
Emanuelli
Monica
M
Pierella
Francesca
F
Volpe
Anna Rita
AR
Astolfi
Paola
P
Carmignani
Marco
M
Fubini
Bice
B
D007611:Aprotinin / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003182:Complement C5 / Q000378:metabolism*; D015936:Complement C5a / Q000378:metabolism; D003460:Crystallization; D003676:Deferoxamine / Q000494:pharmacology; D003855:Deoxyribose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D006801:Humans; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D020842:Plasma Kallikrein / Q000378:metabolism; D012822:Silicon Dioxide / Q000737:chemistry / Q000494:pharmacology*; D019097:Spin Trapping / Q000379:methods; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D003182:Complement C5; D003855:Deoxyribose; D012822:Silicon Dioxide; D015936:Complement C5a; C038983:1,3-dimethylthiourea; D015054:Zymosan; D007611:Aprotinin; D020842:Plasma Kallikrein; D013890:Thiourea; D003676:Deferoxamine