Transfer of human leukocytes into double-knockout Pfp-/-Rag2-/- mice grafted with human skin: increased accumulation of neutrophils in human dermal microvessels.
Severe combined immunodeficient mice reconstituted with human leukocytes have been useful to model parts of the human immune system, including some of its diseases (e.g., AIDS). Because no human polymorphonuclear leukocytes (huPMN) develop in these xenograft models, diseases such as several forms of vasculitis cannot be modeled using this approach. To provide such a model for vasculitis, human skin patches were grafted onto double-knockout Pfp(-/-)Rag2(-/-) mice, which not only lack functional T and B cells but which are also devoid of natural killer cells. After intravenous injection, a high proportion of huPMNs survived within the circulation and accumulated in the human blood vessels. The accumulation increased considerably after the endothelium of the skin patches had been stimulated by tumor necrosis factor-alpha. Alpha mild perivascular neutrophilic infiltration and vascular necrosis was observed in the microvessels of the skin patches. Thus, a xenograft model of vasculitis with predominant huPMNs infiltration has been established for the first time.
Ullrich
Sebastian
S
Department of Rheumatology, University Hospital of Schleswig-Holstein, Campus Lübeck and Rheumaklinik Bad Bramstedt, Ratzeburger Alle 160, 23538 Lübeck, Germany. hsullrich@aol.com
Schumacher
Udo
U
Ai
Maixing
M
Tiemann
Bastian
B
Gay
Steffen
S
Schechner
Jeffery S
JS
Pober
Jordan S
JS
Gross
Wolfgang L
WL
Csernok
Elena
E
D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency*; D005434:Flow Cytometry; D006085:Graft Survival; D006801:Humans; D017708:Leukocyte Transfusion; D008562:Membrane Glycoproteins / Q000172:deficiency*; D051379:Mice; D018345:Mice, Knockout; D008833:Microcirculation / Q000473:pathology*; D009504:Neutrophils / Q000473:pathology*; D009687:Nuclear Proteins; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016038:Skin Transplantation / Q000473:pathology*; D014183:Transplantation, Heterologous / Q000473:pathology*
D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D052899:Pore Forming Cytotoxic Proteins; C499311:RAG2 protein, human; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; D054353:Perforin