Extracellular activities of human granzymes .1. Granzyme a induces IL6 and IL8 production in fibroblast and epithelial cell lines

被引:94
作者
Sower, LE
Klimpel, GR
Hanna, W
Froelich, CJ
机构
[1] NORTHWESTERN UNIV,EVANSTON HOSP,SCH MED,DEPT MED,EVANSTON,IL 60201
[2] UNIV TEXAS,MED BRANCH,DEPT MICROBIOL & IMMUNOL,GALVESTON,TX 77555
关键词
D O I
10.1006/cimm.1996.0187
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Situated in secretory granules of cytotoxic cells, granzymes are essential for induction of target cell apoptosis with perforin. However, since cytotoxic cells constitutively secrete a portion of their synthesized granzymes, these proteases could mediate extracellular functions independently of their role in the lytic event. Thrombin has been shown to function as an activation molecule by cleaving its receptor. We hypothesize that granzymes may act similarly. In this report, we show that purified human granzyme A can induce human lung fibroblasts to produce IL6 and IL8. Cytokine induction is abrogated by treating the serine protease with the suicide serine protease inhibitor 3,4-dichloroisocoumarin. Other fibroblast lines as well as epithelial cells produced cytokines in response to granzyme A. Our data suggest that granzyme A can function as an activation molecule with potentially important immunoregulatory functions. (C) 1996 Academic Press Inc.
引用
收藏
页码:159 / 163
页数:5
相关论文
共 27 条
[1]   INTERLEUKIN-6 IN BIOLOGY AND MEDICINE [J].
AKIRA, S ;
TAGA, T ;
KISHIMOTO, T .
ADVANCES IN IMMUNOLOGY, VOL 54, 1993, 54 :1-78
[2]  
BAGGIOLINI M, 1994, ADV IMMUNOL, V55, P97
[3]  
BARSHAVIT R, 1986, INT REV EXP PATHOL, V29, P213
[4]  
BLEACKLEY RC, 1988, IMMUNOL REV, V10, P5
[5]   ENHANCEMENT OF INCISIONAL WOUND-HEALING AND NEOVASCULARIZATION IN NORMAL RATS BY THROMBIN AND SYNTHETIC THROMBIN RECEPTOR-ACTIVATING PEPTIDES [J].
CARNEY, DH ;
MANN, R ;
REDIN, WR ;
PERNIA, SD ;
BERRY, D ;
HEGGERS, JP ;
HAYWARD, PG ;
ROBSON, MC ;
CHRISTIE, J ;
ANNABLE, C ;
FENTON, JW ;
GLENN, KC .
JOURNAL OF CLINICAL INVESTIGATION, 1992, 89 (05) :1469-1477
[6]  
DAVIE EW, 1975, ANNU REV BIOCHEM, V44, P799
[7]   LOCALIZATION OF INTERLEUKIN-8 IN THE SYNOVIAL-MEMBRANE, CARTILAGE-PANNUS JUNCTION AND CHONDROCYTES IN RHEUMATOID-ARTHRITIS [J].
DELEURAN, B ;
LEMCHE, P ;
KRISTENSEN, M ;
CHU, CQ ;
FIELD, M ;
JENSEN, J ;
MATSUSHIMA, K ;
STENGAARDPEDERSEN, K .
SCANDINAVIAN JOURNAL OF RHEUMATOLOGY, 1994, 23 (01) :2-7
[8]   GRANZYME A-DEFICIENT MICE RETAIN POTENT CELL-MEDIATED CYTOTOXICITY [J].
EBNET, K ;
HAUSMANN, M ;
LEHMANNGRUBE, F ;
MULLBACHER, A ;
KOPF, M ;
LAMERS, M ;
SIMON, MM .
EMBO JOURNAL, 1995, 14 (17) :4230-4239
[9]   THROMBIN-STIMULATED CELL-DIVISION INVOLVES PROTEOLYSIS OF ITS CELL-SURFACE RECEPTOR [J].
GLENN, KC ;
CUNNINGHAM, DD .
NATURE, 1979, 278 (5706) :711-714
[10]  
HAMEED A, 1988, J IMMUNOL, V141, P3142