Transforming growth factor β1 (TGF-β1) induced neutrophil recruitment to synovial tissues

Implications for TGF-β-driven synovial inflammation and hyperplasia

R. A. Fava, Nancy Olsen, A. E. Postlethwaite, K. N. Broadley, J. M. Davidson, L. B. Nanney, C. Lucas, A. S. Townes

Research output: Contribution to journalArticle

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Abstract

We have studied the consequences of introducing human recombinant transforming growth factor β1 (hrTGF-β1) into synovial tissue of the rat, to begin to better understand the significance of the fact that biologically active TGF-β is found in human arthritic synovial effusions. Within 4-6 h after the intra-articular injection of 1 μg of hrTGF-β1 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-β1 at 1-10 fg/ml elicited a chemotactic response from PMNs greater in magnitude than that evoked by FMLP, establishing that TGF-β1 is an effective chemotactic agent for PMNs in vitro as well as in vivo. That PMNs may represent an important source of TGF-β in inflammatory infiltrates was strongly suggested by a demonstration that stored TGF-β1 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/β1 per 109 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-β1 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-β1-induced hyperplasia. Our results demonstrate that TGF-β is capable of exerting pathogenic effects on synovial tissue and that PMNs may represent a significant source of the TGF-β present in synovial effusions.

Original languageEnglish (US)
Pages (from-to)1121-1132
Number of pages12
JournalJournal of Experimental Medicine
Volume173
Issue number5
DOIs
StatePublished - Jan 1 1991

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Neutrophil Infiltration
Transforming Growth Factors
Hyperplasia
Inflammation
Histological Techniques
Intra-Articular Injections
Histocytochemistry
Injections
Tetradecanoylphorbol Acetate
Knee Joint
Autoradiography
Connective Tissue
Thymidine
Arthritis
Neutrophils
Ethanol
Enzyme-Linked Immunosorbent Assay
Cell Proliferation
Acids

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Fava, R. A. ; Olsen, Nancy ; Postlethwaite, A. E. ; Broadley, K. N. ; Davidson, J. M. ; Nanney, L. B. ; Lucas, C. ; Townes, A. S. / Transforming growth factor β1 (TGF-β1) induced neutrophil recruitment to synovial tissues : Implications for TGF-β-driven synovial inflammation and hyperplasia. In: Journal of Experimental Medicine. 1991 ; Vol. 173, No. 5. pp. 1121-1132.
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Transforming growth factor β1 (TGF-β1) induced neutrophil recruitment to synovial tissues : Implications for TGF-β-driven synovial inflammation and hyperplasia. / Fava, R. A.; Olsen, Nancy; Postlethwaite, A. E.; Broadley, K. N.; Davidson, J. M.; Nanney, L. B.; Lucas, C.; Townes, A. S.

In: Journal of Experimental Medicine, Vol. 173, No. 5, 01.01.1991, p. 1121-1132.

Research output: Contribution to journalArticle

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T1 - Transforming growth factor β1 (TGF-β1) induced neutrophil recruitment to synovial tissues

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AU - Olsen, Nancy

AU - Postlethwaite, A. E.

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