Neutrophil chemotaxis in response to TGF-beta isoforms (TGF-beta 1, TGF-beta 2, TGF-beta 3) is mediated by fibronectin.

摘要: TGF-beta isoforms regulate numerous cellular functions including cell growth and differentiation, the synthesis secretion of extracellular matrix proteins, such as fibronectin (Fn), immune response. We have previously shown that 1 is most potent chemoattractant described for human peripheral blood neutrophils (PMNs), suggesting s may play a role in recruitment PMNs during initial phase inflammatory In our current studies, we demonstrate maximal chemotactic response was attained near 40 fM all mammalian isoforms. However, there statistically significant difference migratory distance PMNs: 2 (556 microM) > 3 (463 (380 (beta 2: beta 3, p < or = 0.010; 3: 1, 0.04; 0.0012). A mAb to binding domain (CBD) Fn inhibited by 63% 70%, whereas FMLP, classic chemoattractant, only 18%. contrast, C-terminal epitope did not retard migration (< 1.5%). The Arg-gly-Asp-ser tetrapeptide chemotaxis approximately same extent anti-CBD (52 83%). Furthermore, against VLA-5 integrin (VLA-5; receptor) also TGF-beta-induced chemotaxis. These results indicate mediated interaction sequence CBD with an on PMN surface, primarily integrin. elicited release from PMNs; observed 2.3-fold increase (389 401 ng/ml) supernatants TGF-beta-stimulated compared unstimulated cells (173.6 ng/ml). concentration required cause (4000 fM) at which no longer chemotactic, use constitutively expressed migration. At higher concentrations TGF-beta, released accumulate basal cell, ultimately retarding modulating