| First Author | Kraatz J | Year | 1999 |
| Journal | Shock | Volume | 11 |
| Issue | 1 | Pages | 58-63 |
| PubMed ID | 9921718 | Mgi Jnum | J:52516 |
| Mgi Id | MGI:1329577 | Doi | 10.1097/00024382-199901000-00009 |
| Citation | Kraatz J, et al. (1999) In vitro macrophage endotoxin tolerance: defective in vitro macrophage map kinase signal transduction after LPS pretreatment is not present in macrophages from C3H/HeJ endotoxin resistant mice. Shock 11(1):58-63 |
| abstractText | Altered endotoxin (LPS) signal transduction in macrophages (Mphi) may mediate development of organ dysfunction in sepsis. C3H/HeJ Mphi have a specific genetic defect that renders them tolerant to in vitro LPS activation. LPS tolerance can be induced in normal C3H/HeN Mphi following in vitro LPS pretreatment. In these experiments, in vitro LPS-stimulated activation of Mphi mitogen-activated protein (MAP) kinases were compared in C3H/HeJ and C3H/HeN mice. C3H/HeJ and C3H/HeN Mphi were cultured+/-10 ng/mL LPS pretreatment for 24 h, then stimulated with 0-1,000 ng/mL LPS for 6 h. Western blots were performed on lysates with monoclonal antibody to active ERK1,2 (p42/44), stress-activated protein kinase (SAPK, p54/46), and p38 kinase. Supernatant TNF or IL-1 was determined by bioassay. High dose LPS stimulation activated ERK, SAPK, and p38 kinases in both C3H/HeN and C3H/HeJ Mphi. ERK activation, p46 SAPK, and p38 activation were inhibited in C3H/HeN Mphi after LPS pretreatment, whereas they were unchanged or increased in HeJ Mphi. TNF secretion was significantly decreased in C3H/HeN Mphi following LPS pretreatment, but absent in C3H/HeJ Mphi at all times. Mphi from normal C3H/HeN mice rendered endotoxin tolerant by in vitro, low dose LPS pretreatment have specific signal transduction defects that are not present in genetically LPS hyporesponsive C3H/HeJ mice. |
