title: Transforming growth factor-beta 1 enhances polymorphonuclear leucocyte accumulation in dermal inflammation and transendothelial migration by a priming action.
abstract: Acute inflammatory reactions are usually characterized by polymorphonuclear leucocyte (PMNL) migration into inflamed tissues. Transforming growth factors-beta 1 (TGF-beta 1) may be involved in inflammatory reactions but its actions are controversial and require further in vivo studies. We employed a rabbit dermal inflammation model to investigate the effect of TGF-beta 1 on PMNL migration induced by cytokines and chemotactic factors, using 51Cr-labelled leucocytes to quantify PMNL accumulation in dermal lesions. Injection of TGF-beta 1, over a wide dose range, alone did not elicit PMNL accumulation (0.14 x 10(6) PMNL/site). This contrasted with responses to interleukin-1 alpha (IL-1 alpha) (11.8 x 10(6) PMNL/site), tumour necrosis factor-alpha (TNF-alpha) (4.5), lipopolysaccharide (LPS) (14.9), FNLP (10.1), or IL-8 (6.6). However, when sites were pretreated for 3 hr with TGF-beta 1 (1-10 ng) and subsequently re-injected with the inflammatory stimuli, TGF-beta 1 primed the tissue for an enhanced recruitment of PMNL in response to the endothelium-activating inflammatory agents, IL-1 alpha, TNF-alpha and LPS, but not to IL-8 or FNLP, which are directly PMNL chemotactic. For example, with IL-1 alpha, PMNL accumulation was 205% greater than the additive sum of each response alone (P < 0.05). This was confirmed histologically. TGF-beta 1 pretreatment enhanced PMNL accumulation over a wide dose range of IL-1 alpha and LPS. TGF-beta 1 did not alter the kinetics of IL-1 alpha or LPS-induced PMNL accumulation, but increased the peak rate of accumulation in lesions. Using an in vitro PMNL transendothelial migration system, TGF-beta 1 (10 ng/ml) was found to prime the endothelium for responsiveness to a submaximal dose of IL-1 alpha (0.005 ng/ml) or a threshold dose of LPS (0.01 ng/ml), resulting in enhanced PMNL transendothelial migration. Thus, TGF-beta 1 may have a role in priming the microvasculature for enhanced PMNL emigration, especially in response to endothelium-activating agents.
authors: Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
authors: W T
authors: WT
authors: Drake
authors: A C
authors: AC
authors: Issekutz
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D003872:Dermatitis / Q000473:pathology* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology; D007700:Kinetics; D008233:Lymphotoxin-alpha / Q000494:pharmacology / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D011817:Rabbits; D012867:Skin / Q000473:pathology*
chemical_list: D008233:Lymphotoxin-alpha