INSIGHTS INTO THE MECHANISM BY WHICH INTERFERON-GAMMA IMPROVES MACROPHAGE FUNCTION FOLLOWING HEMORRHAGE AND RESUSCITATION

被引:8
作者
AYALA, A
WANG, P
CHAUDRY, IH
机构
[1] MICHIGAN STATE UNIV,DEPT SURG,SHOCK & TRAUMA RES LABS,E LANSING,MI 48824
[2] MICHIGAN STATE UNIV,DEPT MICROBIOL,SHOCK & TRAUMA RES LABS,E LANSING,MI 48824
[3] MICHIGAN STATE UNIV,DEPT PHYSIOL,SHOCK & TRAUMA RES LABS,E LANSING,MI 48824
关键词
D O I
10.1006/jsre.1993.1051
中图分类号
R61 [外科手术学];
学科分类号
摘要
Recent studies indicate that depressed macrophage (Mφ) immune responses following hemorrhage can be restored by the administration of interferon (IFN)-γ as an adjuvant to resuscitation. However, the mechanism of these effects remains unknown. An important component of the process of Mφ activation in response to pathogens is the mobilization of intracellular calcium ([Ca2+](i)). Since hemorrhage alters the Mφ signal transduction system, the aim of this study, therefore, was to determine whether administration of IFN-γ after hemorrhage restores this mode of macrophage signal transduction. To assess this, C3H/HeN mice were bled to and maintained at a mean blood pressure of 35 mm Hg for 1 hr and then adequately resuscitated. Mice then received either 40,000 units IFN-γ/kg body wt or saline vehicle and were killed 2 hr posthemorrhage to obtain splenic Mφ. These Mφ were loaded with Fluo-3 AM (fluorescent [Ca+2](i) probe) and their capacity to mobilize [Ca2+](i) in response to stimulation with f- met-leu-phe (FMLP; bacterial peptide) was assessed on a laser cytometer. The results indicated that IFN-γ restored the capacity of splenic Mφ to mobilize [Ca2+](i) in response to FMLP. Moreover, the results demonstrated that hemorrhage produced a marked increase in resting cAMP levels in these cells that were lowered to sham levels by the administration of IFN-γ. Thus, it appears that IFN-γ acts to restore Mφ signal transductional capacity, thereby improving Mφ-mediated immune functions following hemorrhage and resuscitation. © 1993 Academic Press. All rights reserved.
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页码:322 / 327
页数:6
相关论文
共 39 条
[1]   EFFECTS OF GRANULOCYTE COLONY-STIMULATING FACTOR IN MODIFYING MORTALITY FROM PSEUDOMONAS-AERUGINOSA PNEUMONIA AFTER HEMORRHAGE [J].
ABRAHAM, E ;
STEVENS, P .
CRITICAL CARE MEDICINE, 1992, 20 (08) :1127-1133
[2]  
Adachi I, 1989, Cytokine, V1, P36, DOI 10.1016/1043-4666(89)91046-6
[3]  
AYALA A, 1991, FASEB J, V5, pA1351
[4]  
AYALA A, 1990, IMMUNOLOGY, V70, P33
[5]   REGULATION OF TRYPANOSOMA-CRUZI INFECTIVITY BY ALPHA-ADRENERGIC AND BETA-ADRENERGIC AGONISTS - DESENSITIZATION PRODUCED BY PROLONGED TREATMENTS OR INCREASING AGONIST CONCENTRATIONS [J].
AYALA, A ;
KIERSZENBAUM, F .
PARASITOLOGY, 1990, 100 :429-434
[6]  
AYALA A, 1990, Cytokine, V2, P170, DOI 10.1016/1043-4666(90)90012-I
[7]  
AYALA A, 1991, J IMMUNOL, V147, P4147
[8]   HEMORRHAGE AND RESUSCITATION - IMMUNOLOGICAL ASPECTS [J].
CHAUDRY, IH ;
AYALA, A ;
ERTEL, W ;
STEPHAN, RN .
AMERICAN JOURNAL OF PHYSIOLOGY, 1990, 259 (04) :R663-R678
[9]  
CHAUDRY IH, 1992, IMMUNOLOGICAL ASPECT
[10]  
ERTEL W, 1991, SURGERY, V110, P440