Is the formation of fibrin a necessary event for the initiation of angiogenic responses in the chick chorioallantoic membrane?

Millipore filters belong to number of solid materials which interact with the chorioallantoic membrane (CAM) and frequently initiate local edemas sometimes accompanied by vascular responses. We observed that such reactions can completely be prevented by coating Millipore filter pieces with hydrophilic polymers (e.g. polyvinylpyrrolidone dextran) or by hydrophobic substances as liquid paraffin and vaseline. Protease inhibitors (Contrikal, epsilon-aminocaproic acid) did not prevent such reactions but increased the incidence of vascular responses. By assaying several blood components we found a relationship between the initiation of vascular responses in the CAM and the process of blood clotting. If small amounts (5 to 10 microliter) of citrated bovine or human plasma arae dropped on the CAM angiogenic responses occur as good as regularly. They are also initiated if the plasmas are recalified and small fibrin fragments are placed on the CAM. Chicken plasma, however, regularly induced such responses only in combination with bovine serum or following application of (or treatment with) fibrinolysis inhibitors. We conclude that the formation of a stable extravascular plasma clot with reduced susceptibility to fibrinolysis could be the most important precondition for the initiation of vascular responses, and that all materials, substances or biofactors capable of activating the clotting cascade should also have the capacity to induce angiogenic responses.