Cell surface regulation of silica-induced apoptosis by the SR-A scavenger receptor in a murine lung macrophage cell line (MH-S).
Scavenger receptors (SR) are responsible for recognition of ligands as diverse as oxidized LDL (endogenous) to respirable particulates (exogenous). A number of recent studies have suggested that these SR ligands induce apoptosis of macrophages. However, the mechanism by which SR triggers apoptosis is not understood. This study used a murine alveolar macrophage cell line (MH-S) to investigate the role of the SR in caspase activation. The presence of SR on MH-S cells was confirmed by FACS analysis and was similar to the distribution found on murine alveolar macrophages. The activity of caspases 1, 3, and 6 was measured following a 6-h exposure to crystalline silica with and without blockers of the SR. Caspase activities were determined by hydrolysis of specific chromogenic substrates and formation of an active enzymatic form (Western for active caspase 3). Silica stimulated significant caspase activity, apoptosis, and necrosis of MH-S cells, which was attenuated by 2F8 (a blocking antibody) and polyinosinic acid (a nonspecific SR antagonist). The results indicate that the SR are necessary for caspase activation and subsequent apoptosis (as well as necrosis) caused by silica in macrophage cells.
Chao
S K
SK
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Texas Houston Health Science Center, Houston, Texas 77030, USA.
Hamilton
R F
RF
Pfau
J C
JC
Holian
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry; D053938:DNA Fragmentation; D004789:Enzyme Activation; D005434:Flow Cytometry; D016676:Macrophages, Alveolar / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D008565:Membrane Proteins; D051379:Mice; D009336:Necrosis; D011971:Receptors, Immunologic / Q000032:analysis / Q000502:physiology*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D012822:Silicon Dioxide / Q000494:pharmacology*
D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D012822:Silicon Dioxide; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases