Interaction of Fibronectin (FN) Cell Binding Fragments and Interleukin-8 (IL-8) in Regulating Neutrophil Chemotaxis

Mechanical loading and injury induce human myotubes to release neutrophil chemoattractants

“…In addition, rhIL-8 at concentrations of IL-8 observed in conditioned media failed to elicit neutrophil chemotaxis. These later observations are consistent with previous investigators who demonstrated that rhIL-8 causes neutrophil chemotaxis at much higher concentrations (ϳ10 ng/ml-80 g/ml) than concentrations of IL-8 observed in our conditioned media (10 -70 pg/ml) (23,24). Because TGF-␤1, a potent neutrophil chemoattractant and a modest activator of ROS production from adherent neutrophils (3,42), has been reported to inhibit the synthesis of IL-8 (44), we then measured TGF-␤1.…”

“…trations that were observed in conditioned media and a concentration that has been reported to elicit neutrophil chemotaxis (5,17,23,24,42). Positive control concentrations of both rhIL-8 (100 ng/ml) and hTGF-␤1 (10 pg/ml) elicited chemotaxis indexes (62.4 Ϯ 9.4 and 27.6 Ϯ 10.0, respectively) that were significantly higher than an index of zero.…”

Heterologous desensitization of IL-8-mediated chemotaxis in human neutrophils by a cell-binding fragment of fibronectin

“…In this study, we demonstrated that incubation of neutrophils with a ␤ 1 integrin-activating antibody (TS2/16) mimicked the effects of the cell-binding FN fragment, whereas incubation with a blocking antibody to the ␤ 1 integrin (mAb13) reversed the inhibitory effect of the 120-kDa FN fragment on IL-8-mediated chemotaxis. Because the interaction between cell-binding fragments of FN and neutrophils in inhibiting IL-8-mediated chemotaxis was dependent on the RGD domain of FN [14], we also examined the ability of the ␤ 3 -like integrin, LRI, to be possibly involved in the inhibitory effect on IL-8-mediated chemotaxis. We demonstrated that incubating neutrophils with the blocking antibody to LRI (7G2) also resulted in the reversal of the inhibitory effect of the 120-kDa FN on IL-8-mediated chemotaxis.…”

“…Our previous studies have shown that incubation of human neutrophil suspensions with increasing concentrations of a 120-kDa cell-binding fragment of FN (120-kDa FN) resulted in a dose-dependent inhibition of IL-8-mediated chemotaxis [14]. In this study, we examined whether the observed inhibition of IL-8-mediated chemotaxis by a 120-kDa FN cell-binding fragment was specific for IL-8 receptors or included other seven-transmembrane-spanning G-protein-coupled neutrophil chemoattractant receptors, such as N-formyl-methionyl-leucylphenylalanine (fMLP) and C5a receptors.…”

Neutrophil haptotaxis induced by mouse MNCF: interactions with extracellular matrix glycoproteins probably contribute to overcoming the anti-inflammatory action of dexamethasone

“…Adhesion to fi bronectin is considered to have an important functional impact since cytokines such as GM-CSF and CXCL8, which do not activate neutrophils in suspension, are allowed to become powerful stimulatory agents when they interact with fi bronectin-adherent cells [38]. In addition, fi bronectin cell-binding fragments are able to inhibit the CXCL8-induced neutrophil migration [39]. In fact, we have shown here that DX-treated neutrophils lose their capacity to adhere to fi bronectin, which could account for the absence of CXCL8-induced DX-treated neutrophil migration in the presence of ECM.…”