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

被引:27
作者
Kraatz, J [1 ]
Clair, L [1 ]
Rodriguez, JL [1 ]
West, MA [1 ]
机构
[1] Univ Minnesota, Hennepin Cty Med Ctr, Dept Surg, Minneapolis, MN 55415 USA
来源
SHOCK | 1999年 / 11卷 / 01期
关键词
D O I
10.1097/00024382-199901000-00009
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Altered endotoxin (LPS) signal transduction in macrophages (M phi) may mediate development of organ dysfunction in sepsis. C3H/HeJ M phi have a specific genetic defect that renders them "tolerant" to in vitro LPS activation. LPS tolerance can be induced in normal C3H/HeN M phi following in vitro LPS pretreatment. In these experiments, in vitro LPS-stimulated activation of M phi mitogen-activated protein (MAP) kinases were compared in C3H/HeJ and C3H/HeN mice. C3H/HeJ and C3H/HeN M phi 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-l was determined by bioassay. High dose LPS stimulation activated ERK, SAPK, and p38 kinases in both C3H/HeN and C3H/HeJ M phi, ERK activation, p46 SAPK, and p38 activation were inhibited in C3H/HeN M phi after LPS pretreatment, whereas they were unchanged or increased in HeJ M phi. TNF secretion was significantly decreased in C3H/HeN M phi following LPS pretreatment, but absent in C3H/HeJ M phi at all times. M phi 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.
引用
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页码:58 / 63
页数:6
相关论文
共 35 条
[1]  
AGGARWAL BB, 1985, METHOD ENZYMOL, V116, P441
[2]   MULTIPLE ORGAN FAILURE SYNDROME IN THE 1990S - SYSTEMIC INFLAMMATORY RESPONSE AND ORGAN DYSFUNCTION [J].
BEAL, AL ;
CERRA, FB .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1994, 271 (03) :226-233
[3]   EFFECT OF GAMMA-INTERFERON ON CACHECTIN EXPRESSION BY MONONUCLEAR PHAGOCYTES - REVERSAL OF THE LPSD (ENDOTOXIN RESISTANCE) PHENOTYPE [J].
BEUTLER, B ;
TKACENKO, V ;
MILSARK, I ;
KROCHIN, N ;
CERAMI, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 1986, 164 (05) :1791-1796
[4]  
Bone RC, 1994, CRIT CARE MED, V22, P8
[5]   TUMOR-CELL KILLING AND CYTOSTASIS BY C3H-HEJ MACROPHAGES ACTIVATED INVITRO BY LIPID A-ASSOCIATED PROTEIN AND INTERFERON-GAMMA [J].
CHAPES, SK ;
KILLION, JW ;
MORRISON, DC .
JOURNAL OF LEUKOCYTE BIOLOGY, 1988, 43 (03) :232-237
[6]   ENDOTOXIN TOLERANCE - EFFECTS ON LETHALITY AND MACROPHAGE THROMBOXANE-(B(2)) AND INTERLEUKIN-6 PRODUCTION [J].
CHEN, H ;
HALUSHKA, PV ;
COOK, JA .
SHOCK, 1994, 1 (05) :366-371
[7]   MACROPHAGES DERIVED FROM C3H/HEJ (LPS(D)) MICE RESPOND TO BACTERIAL LIPOPOLYSACCHARIDE BY ACTIVATING NF-KAPPA-B [J].
DING, AH ;
HWANG, SY ;
LANDER, HM ;
XIE, QW .
JOURNAL OF LEUKOCYTE BIOLOGY, 1995, 57 (01) :174-179
[8]  
GLAUSER MP, 1994, CLIN INFECT DIS S2, V18, P205
[9]   LIPOPOLYSACCHARIDE (LPS)-BINDING PROTEIN ACCELERATES THE BINDING OF LPS TO CD14 [J].
HAILMAN, E ;
LICHENSTEIN, HS ;
WURFEL, MM ;
MILLER, DS ;
JOHNSON, DA ;
KELLEY, M ;
BUSSE, LA ;
ZUKOWSKI, MM ;
WRIGHT, SD .
JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 179 (01) :269-277
[10]   A MAP KINASE TARGETED BY ENDOTOXIN AND HYPEROSMOLARITY IN MAMMALIAN-CELLS [J].
HAN, J ;
LEE, JD ;
BIBBS, L ;
ULEVITCH, RJ .
SCIENCE, 1994, 265 (5173) :808-811