Am. J. Respir. Cell Mol. Biol., Vol 12, No. 5, 05 1995, 540-546.
Alveolar macrophages from C3H/HeJ mice show sensitivity to endotoxin
LK Ryan and MW Vermeulen
Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, USA.
Alveolar macrophages (AM) orchestrate the release of several cytokines in
the lung, including tumor necrosis factor alpha (TNF). Lipopolysaccharide
endotoxin (LPS), one of the most potent stimulators of TNF production in
macrophages, often contributes to the development of adult respiratory
distress syndrome. The mechanism by which LPS induces TNF production in
macrophages is unclear. Many studies have employed murine macrophages
lavaged from the peritoneal cavity (PM), either resident cells or those
obtained following elicitation with sterile thioglycollate (TGPM), as these
cells are readily accessible. LPS does not induce TNF in PM or TGPM from
C3H/HeJ mice, and the alteration is thought to reside at the
post-transcriptional level of gene regulation. Generalization of results
from PM to AM may not be warranted, however. While investigating cytokine
production by AM cell lines, we observed that C3HAMSV40, a transformed cell
line derived from C3H/HeJ AM, made substantial quantities of TNF when
stimulated with 1 microgram/ml LPS, prompting us to study TNF production in
primary C3H/HeJ AM. In the present study, readily detectable quantities of
biologically active TNF were found in supernatants of C3H/HeJ AM that had
been stimulated in vitro with 0.01 to 10 micrograms/ml LPS. The amount of
TNF produced was not significantly different from that observed with AM
from endotoxin-sensitive C3HeB/FeJ mice. LPS induction of TNF in AM from
either mouse strain was completely inhibited by polymyxin B, demonstrating
that the sensitivity of C3H/HeJ AM was not due to a contaminant in the
LPS.(ABSTRACT TRUNCATED AT 250 WORDS)
