The initiator of coagulation, full-length tissue factor (flTF), in complex with factor VIIa, influences angiogenesis through PAR-2. Recently, an alternatively spliced variant of TF (asTF) was discovered, in which part of the TF extracellular domain, the transmembrane, and cytoplasmic domains are replaced by a unique C terminus. Subcutaneous tumors produced by asTF-secreting cells revealed increased angiogenesis, but it remained unclear if and how angiogenesis is regulated by asTF. Here, we show that asTF enhances angiogenesis in matrigel plugs in mice, whereas a soluble form of flTF only modestly enhances angiogenesis. asTF dose-dependently upregulates angiogenesis ex vivo independent of either PAR-2 or VIIa. Rather, asTF was found to ligate integrins, resulting in downstream signaling. asTF-␣V3 integrin interaction induces endothelial cell migration, whereas asTFdependent formation of capillaries in vitro is dependent on ␣61 integrin. Finally, asTF-dependent aortic sprouting is sensitive to 1 and 3 integrin blockade and a TF-antibody that disrupts asTFintegrin interaction. We conclude that asTF, unlike flTF, does not affect angiogenesis via PAR-dependent pathways but relies on integrin ligation. These findings indicate that asTF may serve as a target to prevent pathological angiogenesis.cancer ͉ coagulation ͉ endothelial cells ͉ integrins
Little information is available on the influence of chemical growth regulators on warm season perennial turf grasses. Therefore, greenhouse and field experiments were conducted to evaluate several such compounds for their potential in retarding the growth of common and ‘Sunturf’ bermudagrass [Cynodon dactylon (L.) Pers]. Maleic hydrazide [ 1,2‐dihydro‐3,6 pyridazinedione (MH)] and chlorflurenol [Methyl‐2‐chloro‐9‐hydroxyfluorene‐9‐carboxylate (CF)] injured both types when applied at 4.5 or 3.4 kg/ha in the greenhouse. Ethephon (2‐chloro‐ethylphosphonic acid) stimulated stem elongation of both bermudagrasses when applied at rates below 6.7 kg/ha in the greenhouse, while higher concentration retarded their growth in the field. Greenhouse plants grown under a wet regime (watered daily) showed no significant difference in chemical retardant effects on plant top growth and internode length from those grown under a dry (watered every three days) regime. Although more plant growth did occur in wet regimes, the growth retardation effect by the chemicals was not nullified by such conditions. Common bermudagrass was less susceptible to injury than Sunturf in the greenhouse, and no significant retardation of Sunturf top growth was obtained in the field. Fluoridamid (N[3‐[(1,1,1‐trifluoromethylsulfonyl) amino]4‐methylphenyl]acetamide), MBR 12325 (N‐[2,4dimethyl‐5‐[ trifluoro‐methyl)‐sulfonyl] ‐amino]‐phenyl acetamide), MH, CF, and ethephon were effective in reducing bermudagrass vegetative growth and seedhead development in the field. Single high rates of these compounds frequently caused bermudagrass injury, while split applications or chemical combinations at low rates provided excellent growth retardation with no undesirable turf appearance.
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