Selective binding of platelet factor 4 to regions of active angiogenesis in vivo. Hansell, Peter, Theodore E. Maione, Per Borgstr[diaeresis]om. La Jolla Institute for Experimental Medicine, La Jolla, CA 92037, USA Repligen Corporation, Cambridge, MA 02139, USA, Present address: Department of Physiology & Medical Biophysics, Biomedical Center, University of Uppsala, S-751 23 Uppsala, Sweden
APStracts 2:0130H, 1995.
In a previous study we suggested that rhPF4 preferentially binds in vivo to regions of active angiogenesis/endothelial cell migration. To test this hypothesis, binding of fluorescently labeled rhPF4 to newly formed vessels was compared to that of the normal skin vasculature, using syngeneic Langerhans islets as inducers of angiogenesis. Islets were implanted in the dorsal skinfold chamber of the hamster and the binding of rhPF4 was studied using intravital fluorescence microscopy. Intra-arterially injected rhPF4 labeled, with high intensity, the endothelium along newly formed vessels of the islets (1,632 +/- 617 _m labeled vessel length per islet) and only on rare occasions (1 +/- 2 site per cm2 skinfold) were short (62 +/- 48 _m) intense labeled sites found in the normal vasculature of the skinfold. Heparin could displace most of the label if injected within 10 min after the rhPF4-injection but not 30 min after. In conclusion, rhPF4 preferentially binds to regions of active angiogenesis in vivo. Upon binding, rhPF4 is internalized as judged from a decreasing heparin sensitivity with time after rhPF4 injection. The infrequent rhPF4 labeling sites in the normal skin vasculature most likely represent regions of newly formed cells/migration, i.e. normal endothelial turnover, supporting our previous findings demonstrating that the occurrence of such regions is rare in the normal microvasculature. Furthermore, in spite of the previously demonstrated short half-life in plasma, systemically injected rhPF4 will target regions regions of angiogenesis with high affinity thereby facilitating the anti-angiogenic effect of PF4. 

Received 25 January 1995; accepted in final form 10 March 1995.
APS Manuscript Number H72-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 April 1995.