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 language | English (US) |
|---|---|
| Pages (from-to) | 1121-1132 |
| Number of pages | 12 |
| Journal | Journal of Experimental Medicine |
| Volume | 173 |
| Issue number | 5 |
| DOIs | |
| State | Published - Jan 1 1991 |
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All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Immunology
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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 journal › Article
TY - JOUR
T1 - Transforming growth factor β1 (TGF-β1) induced neutrophil recruitment to synovial tissues
T2 - Implications for TGF-β-driven synovial inflammation and hyperplasia
AU - Fava, R. A.
AU - Olsen, Nancy
AU - Postlethwaite, A. E.
AU - Broadley, K. N.
AU - Davidson, J. M.
AU - Nanney, L. B.
AU - Lucas, C.
AU - Townes, A. S.
PY - 1991/1/1
Y1 - 1991/1/1
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.173.5.1121
DO - 10.1084/jem.173.5.1121
M3 - Article
VL - 173
SP - 1121
EP - 1132
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 5
ER -