INHIBITION BY RECOMBINANT SLPI AND HALF-SLPI (ASN55-ALA107) OF ELASTASE AND CATHEPSIN-G ACTIVITIES - CONSEQUENCE FOR NEUTROPHIL-PLATELET COOPERATION

被引:33
作者
RENESTO, P [1 ]
BALLOY, V [1 ]
KAMIMURA, T [1 ]
MASUDA, K [1 ]
IMAIZUMI, A [1 ]
CHIGNARD, M [1 ]
机构
[1] TEIJIN INST BIOMED RES, BIOMOLEC CHEM LAB, TOKYO, JAPAN
关键词
LEUKOCYTES; PLATELETS; CATHEPSIN-G; ELASTASE; SECRETORY LEUKOCYTE PROTEINASE INHIBITOR (SLPI); 1/2; SLPI;
D O I
10.1111/j.1476-5381.1993.tb13511.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 The capacity of recombinant human secretory leukocyte proteinase inhibitor (SLPI) to inhibit human leukocyte elastase (HLE) and cathespin G (Cat G) was investigated and compared with a recombinant truncated form (carboxyl-terminal domain, Asn55-Ala107) called 1/2 SLPI. 2 Both compounds were efficient when tested against enzymatic activities of purified HLE and Cat G indicating that the HLE- and Cat G-inhibitory sites were preserved in the truncated form. SLPI and 1/2 SLPI also affected platelet activation induced by 0.2 muM Cat G (IC50 = 112 +/- 13 nm for SLPI and 280 +/- 12 nm for 1/2 SLPI). 3 The effects of SLPI and 1/2 SLPI were then tested against polymorphonuclear neutrophil (PMN)-mediated platelet activation, a cell-to-cell interaction mediated by HLE and Cat G released from PMN. In this experimental system, addition of SLPI or 1/2 SLPI before N-formyl-Met-Leu-Phe (fMLP) led to the inhibition of the resulting platelet activation. As was the case for Cat G enzymatic activity and Cat G-induced platelet activation, SLPI was more efficient than 1/2 SLPI (IC50 = 676 +/- 69 nm vs 1121 +/- 150 nm). 4 The ratio of the IC50 against PMN-mediated platelet activation compared to purified Cat G-mediated platelet activation was 6.03 for SLPI and 4.32 for 1/2 SLPI. This difference may be due to the smaller size of the truncated form which could allow this molecule to diffuse more easily between PMN and platelets. 5 In conclusion, 1/2 SLPI could be a promising candidate in the treatment of pathological states linked to inflammation in which participation of HLE and Cat G has been evoked.
引用
收藏
页码:1100 / 1106
页数:7
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