TY - JOUR
T1 - Aminopeptidase A is a constituent of activated pericytes in angiogenesis
AU - Schlingemann, Reinier O.
AU - Oosterwijk, Egbert
AU - Wesseling, Pieter
AU - Rietveld, Frank J.R.
AU - Ruiter, Dirk J.
PY - 1996
Y1 - 1996
N2 - 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.
AB - 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.
KW - Aminopeptidase A
KW - Angiogenesis
KW - MAb RC38
KW - Pericytes
KW - Tumours
KW - Wound healing
UR - http://www.scopus.com/inward/record.url?scp=0029793759&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1096-9896(199608)179:4<436::AID-PATH611>3.0.CO;2-A
DO - 10.1002/(SICI)1096-9896(199608)179:4<436::AID-PATH611>3.0.CO;2-A
M3 - Article
C2 - 8869294
AN - SCOPUS:0029793759
SN - 0022-3417
VL - 179
SP - 436
EP - 442
JO - Journal of Pathology
JF - Journal of Pathology
IS - 4
ER -