Silica induced suppression of the production of third and fifth components of the complement system by human lung cells in vitro.
Although investigations to date have demonstrated the ability of the monocyte/macrophage to synthesize complement components, only a limited number of studies on complement synthesis by nonhepatic tissue cells have been reported. To begin to fill this gap in our knowledge we have recently evaluated the ability of lung tissue cells to synthesize and secrete various complement components in vitro. Using 35S-methionine incorporation and immunoprecipitation techniques we have previously demonstrated the ability human lung type II pneumocytes (A549) and human lung fibroblasts (WI-38), to synthesize and secrete a variety of both early and terminal complement components, as well as several regulatory proteins including Clr, Cls, C4, C3, C5, C6, C7, C8, C9, Factor B, Factor H, Factor I and Cls inactivator. Our present studies demonstrate the capability of silica to regulate complement component production by A549 cells, but not complement component production by WI-38 cells. Specifically, using sensitive ELISAs we demonstrated that a non-toxic dose of silica had the capability to suppress the production of both C3 and C5 by A549 pneumocytes by 40-50 percent, but had no effect on C3 or C5 synthesis by WI-38 fibroblasts. Additionally, using 35S-methionine incorporation and TCA precipitation techniques, we demonstrated that suppression of C3 and C5 production by silica treated A549 pneumocytes was not a result of suppression of total protein synthesis. These studies demonstrate that silica, which has been implicated in pulmonary diseases, has the capability to regulate local complement production by lung tissue cells in vitro. In vivo, this suppression of complement production by the type II pneumocytes could alter the local tissue reservoir of complement components during infection and pulmonary injury, thus resulting in depressed pulmonary host defense.
Rothman
B L
BL
Department of Pathology, University of Connecticut Health Center, Farmington.
Contrino
J
J
Merrow
M
M
Despins
A
A
Kennedy
T
T
Kreutzer
D L
DL
D002460:Cell Line; D002470:Cell Survival; D003176:Complement C3 / Q000096:biosynthesis*; D003182:Complement C5 / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects; D012822:Silicon Dioxide / Q000633:toxicity*
D003176:Complement C3; D003182:Complement C5; D011506:Proteins; D012822:Silicon Dioxide