In vivo targeting of integrin receptors in human skin xenografts by intravenously applied antibodies.
We examined whether systemically injected monoclonal antibodies (mAbs) directed to cell-surface glycoproteins of human keratinocytes reach their target antigens in xenograft transplants of normal human skin on SCID mice. The integrins alpha 6 beta 4, expressed in the basal cell layer of human epidermis, and glycoprotein T16 (gp 40/50), expressed in terminally differentiating keratinocytes of the stratum spinosum, were selected as targets. It was found that all injected mAbs selectively localized to their antigens and bound and saturated their targets even in the uppermost layers of the stratum malpighii. This could easily be monitored by direct immunofluorescence staining since SCID mice lack endogenous production of significant amounts of immunoglobulins. After a single injection, mAbs could still be detected at the target site after 14 days. Our results proved that heterologous immunoglobulins pass systemic capillary filters in this xenograft model and specifically bind to their target molecules. Thus, xenografted SCID mice provide a versatile model for studying cell-surface glycoprotein-mediated interactions by the use of functionally interfering antibodies under in vivo conditions in human skin.
Kaufmann
R
R
Department of Dermatology, University of Ulm, Germany.
Hainzl
A
A
Sterry
W
W
Alberti
S
S
Klein
C E
CE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000378:metabolism; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D016023:Integrins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D051381:Rats; D016038:Skin Transplantation / Q000276:immunology*; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D016023:Integrins