TRANSFORMING GROWTH-FACTOR BETA-1 (TGF-BETA-1) INDUCED NEUTROPHIL RECRUITMENT TO SYNOVIAL TISSUES - IMPLICATIONS FOR TGF-BETA-DRIVEN SYNOVIAL INFLAMMATION AND HYPERPLASIA

被引:198
作者
FAVA, RA
OLSEN, NJ
POSTLETHWAITE, AE
BROADLEY, KN
DAVIDSON, JM
NANNEY, LB
LUCAS, C
TOWNES, AS
机构
[1] VANDERBILT UNIV, MED CTR, SCH MED, DEPT MED, NASHVILLE, TN 37232 USA
[2] VANDERBILT UNIV, MED CTR, SCH MED, DEPT CELL BIOL & BIOCHEM, NASHVILLE, TN 37232 USA
[3] VANDERBILT UNIV, MED CTR, SCH MED, DEPT PATHOL, NASHVILLE, TN 37232 USA
[4] VANDERBILT UNIV, MED CTR, SCH MED, DEPT PLAST SURG, NASHVILLE, TN 37232 USA
[5] UNIV TENNESSEE, CTR HLTH SCI, DEPT MED, MEMPHIS, TN 38163 USA
[6] UNIV TENNESSEE, CTR HLTH SCI, DIV CONNECT TISSUE DIS, MEMPHIS, TN 38163 USA
[7] DEPT VET AFFAIRS MED CTR, MEMPHIS, TN 38163 USA
[8] GENENTECH INC, DEPT MED & ANALYT CHEM, SAN FRANCISCO, CA 94080 USA
关键词
D O I
10.1084/jem.173.5.1121
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We have studied the consequences of introducing human recombinant transforming growth factor beta-1 (hrTGF-beta-1) into synovial tissue of the rat, to begin to better understand the significance of the fact that biologically active TGF-beta is found in human arthritic synovial effusions. Within 4-6 h after the intra-articular injection of 1-mu-g of hrTGF-beta-1 into rat knee joints, extensive recruitment of polymorphonuclear leukocytes (PMNs) was observed. Cytochemistry and high resolution histological techniques were used to quantitate the influx of PMNs, which peaked 6 h post-injection. In a Boyden chamber assay, hrTGF-beta-1 at 1-10 fg/ml elicited a chemotactic response from PMNs greater in magnitude than that evoked by FMLP, establishing that TGF-beta-1 is an effective chemotactic agent for PMNs in vitro as well as in vivo. That PMNs may represent an important source of TGF-beta in inflammatory infiltrates was strongly suggested by a demonstration that stored TGF-beta-1 was secreted during phorbol myristate acetate-stimulated degranulation in vitro. Acid/ethanol extracts of human PMNs assayed by ELISA contained an average of 355 ng of TGF/beta-1 per 10(9) cells potentially available for secretion during degranulation of PMNs. [H-3]Thymidine incorporation in vivo and autoradiography of tissue sections revealed that widespread cell proliferation was triggered by TGF-beta-1 injection. Synovial lining cells and cells located deep within the subsynovial connective tissue were identified as sources of at least some of the new cells that contribute to TGF-beta-1-induced hyperplasia. Our results demonstrate that TGF-beta is capable of exerting pathogenic effects on synovial tissue and that PMNs may represent a significant source of the TGF-beta present in synovial effusions.
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收藏
页码:1121 / 1132
页数:12
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