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 microgram 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. [3H]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.
Article|
May 01 1991
Transforming growth factor beta 1 (TGF-beta 1) induced neutrophil recruitment to synovial tissues: implications for TGF-beta-driven synovial inflammation and hyperplasia.
R A Fava,
R A Fava
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
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N J Olsen,
N J Olsen
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
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A E Postlethwaite,
A E Postlethwaite
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
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K N Broadley,
K N Broadley
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
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J M Davidson,
J M Davidson
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
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L B Nanney,
L B Nanney
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
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C Lucas,
C Lucas
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
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A S Townes
A S Townes
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
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R A Fava
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
N J Olsen
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
A E Postlethwaite
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
K N Broadley
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
J M Davidson
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
L B Nanney
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
C Lucas
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
A S Townes
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1991) 173 (5): 1121–1132.
Citation
R A Fava, N J Olsen, A E Postlethwaite, K N Broadley, J M Davidson, L B Nanney, C Lucas, A S Townes; Transforming growth factor beta 1 (TGF-beta 1) induced neutrophil recruitment to synovial tissues: implications for TGF-beta-driven synovial inflammation and hyperplasia.. J Exp Med 1 May 1991; 173 (5): 1121–1132. doi: https://doi.org/10.1084/jem.173.5.1121
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