Aminopeptidase a is a constituent of activated pericytes in angiogenesis.
Monoclonal antibody (MAb) RC38 recognizes a human renal antigen of 160 kD recently identified as human aminopeptidase A (APA; EC 3.4.11.7). This ectoenzyme is able to hydrolyse selectively N-terminal glutamyl and aspartyl residues from oligopeptides. By enzyme histochemistry, APA activity has also been localized in the microvessels of all organs in animals and man. The purpose of this study was to investigate the distribution of human APA as recognized by MAb RC38 in the microvasculature of normal human tissues and pathological conditions associated with neovascularization. Unexpectedly, in normal tissues vascular staining with MAb RC38 was generally weak and often absent, while in tumours, granulation tissue, and chronic synovitis, marked microvascular staining was demonstrated. By immuno-electron microscopy, the antigen was found on the cell membrane of activated pericytes and their processes in the tumour vasculature. RC38 expression could not be detected on cultured human endothelial cells or pericytes. These observations suggest that pericyte expression of a subtype of APA (as recognized by MAb RC38) is markedly enhanced in the vasculature of tumours and wound healing tissue as compared with normal resting tissues. This provides further evidence of the altered state of pericytes in these conditions. Pericyte APA may be involved in the metabolism of biologically active oligopeptides during neovascularization, supporting a regulatory role of pericytes in this process. In addition, MAb RC38 may be useful as a marker of pericyte activation in tissue sections.
Schlingemann
R O
RO
Department of Ophthalmology, University of Amsterdam, Netherlands.
Oosterwijk
E
E
Wesseling
P
P
Rietveld
F J
FJ
Ruiter
D J
DJ
D000626:Aminopeptidases / Q000378:metabolism*; D001943:Breast Neoplasms / Q000098:blood supply; D018929:Cell Culture Techniques; D003110:Colonic Neoplasms / Q000098:blood supply; D005260:Female; D043384:Glutamyl Aminopeptidase; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008833:Microcirculation / Q000201:enzymology; D016253:Microscopy, Immunoelectron; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000201:enzymology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology
D000626:Aminopeptidases; D043384:Glutamyl Aminopeptidase