Effect of lipopolysaccharide on C3 and C5 production by human lung cells.
Although studies to date have demonstrated the ability of the monocyte/macrophage to produce C components in vitro, very few studies on C production by nonhepatic tissue cells have been reported. Recently, using 35S-methionine incorporation and immunoprecipitation techniques our laboratory has demonstrated the ability of tissue cells, i.e., the human lung type II pneumocyte (A549) and human lung fibroblast (WI-38), to synthesize and secrete a variety of early and terminal complement components, as well as several regulatory proteins in vitro, i.e., C1r, C1s, C4, C3, C5, C6, C7, C8, C9, factor B, factor H, factor I, and C1s inactivator. In our studies, we extended these observations by demonstrating the capability of LPS to modulate C3 production by A549 pneumocytes. Specifically, using a sensitive ELISA we demonstrated that A549 pneumocytes exposed to LPS induced an 80 to 180% increase in C3 levels when compared to untreated A549 cells. Interestingly, LPS had no effect on C5 production or total protein synthesis by A549 pneumocytes. In the case of the WI-38 fibroblast, LPS had no effect on 1) C3 production, 2) C5 production, or 3) total protein synthesis in vitro. These studies demonstrate that agents such as LPS have the potential to selectively regulate C production (i.e., C3) in individual lung cells in vitro, and suggests that in vivo LPS may alter the local tissue reservoir of C components during infection and lung injury, thus impacting on pulmonary inflammation and host defense.
Rothman
B L
BL
Department of Pathology, University of Connecticut Health Center, Farmington 06032.
Merrow
M
M
Despins
A
A
Kennedy
T
T
Kreutzer
D L
DL
D000818:Animals; D002417:Cattle; D002460:Cell Line; D003176:Complement C3 / Q000096:biosynthesis* / Q000378:metabolism; D003182:Complement C5 / Q000096:biosynthesis* / Q000378:metabolism; D005312:Fetal Blood / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology* / Q000633:toxicity; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014176:Protein Biosynthesis
D003176:Complement C3; D003182:Complement C5; D008070:Lipopolysaccharides