Circulating TIE2⁺ monocytes migrate toward Ang-2 and have marked proangiogenic activity in vivo. (A) Modified Boyden chamber assays show migration of resident monocytes toward Ang-2. The 2 graphics show parts of 2 independent experiments of 3 performed. Both serum and Ang-2 induced significant migration of resident monocytes (left histograms; P < .05 vs control: Medium). Heat inactivation of Ang-2 or treatment of the cells with neutralizing anti-TIE2 antibodies, but not with control immunoglobulins, abrogates cell migration in response to Ang-2 (right histograms). (B) Human glioma U87 cells were injected subcutaneously into nude mice with or without the indicated monocyte populations at a 1:100 or 1:20 ratio. Tumors were grown for 5 to 7 days and analyzed by CD31 immunostaining and confocal analysis to assess angiogenesis. Representative pictures of the tumors are shown. The tumor margin is indicated by a dashed line. (C) The mean vascular area (n = 3 tumors/group) was calculated by digital image analysis and expressed as fold increase over the value obtained in tumors from U87 cells only. Error bars indicate SD. Statistical difference between groups was calculated by Student t test.