title: Transforming growth factor beta 1 (TGF-beta 1) induced neutrophil recruitment to synovial tissues: implications for TGF-beta-driven synovial inflammation and hyperplasia.
abstract: 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.
authors.affiliation: Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: R A
authors.initials: RA
authors.lastname: Fava
authors.forename: N J
authors.initials: NJ
authors.lastname: Olsen
authors.forename: A E
authors.initials: AE
authors.lastname: Postlethwaite
authors.forename: K N
authors.initials: KN
authors.lastname: Broadley
authors.forename: J M
authors.initials: JM
authors.lastname: Davidson
authors.forename: L B
authors.initials: LB
authors.lastname: Nanney
authors.forename: C
authors.initials: C
authors.lastname: Lucas
authors.forename: A S
authors.initials: AS
authors.lastname: Townes
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000502:physiology; D004247:DNA / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006965:Hyperplasia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D007270:Injections, Intra-Articular; D008854:Microscopy, Electron; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013583:Synovial Membrane / Q000187:drug effects / Q000503:physiopathology* / Q000648:ultrastructure; D013585:Synovitis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D013936:Thymidine / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology*; D014316:Tritium
chemical_list: D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014316:Tritium; D009240:N-Formylmethionine Leucyl-Phenylalanine; D004247:DNA; D013936:Thymidine