Alveolar macrophages from C3H/HeJ mice show sensitivity to endotoxin.
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)
Ryan
L K
LK
Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, USA.
Vermeulen
M W
MW
D000818:Animals; D002472:Cell Transformation, Viral; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D011112:Polymyxin B / Q000494:pharmacology; D013539:Simian virus 40; D013864:Thioglycolates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004731:Endotoxins; D008070:Lipopolysaccharides; D013864:Thioglycolates; D014409:Tumor Necrosis Factor-alpha; D011112:Polymyxin B