Resolution of cutaneous inflammation after local elimination of macrophages.
We constructed an immunotoxin, composed of an antibody directed against the high-affinity IgG receptor CD64 and Ricin-A, with the aim of resolving chronic inflammation through elimination of activated macrophages. In vitro, this immunotoxin proved very efficient in inducing apoptosis in activated macrophages, leaving resting and low CD64-expressing macrophages unaffected. We examined the activity of our immunotoxin in a sodium lauryl sulfate (SLS)-induced cutaneous inflammation model, using transgenic mice expressing human CD64. Upon intradermal injection of the immunotoxin (IT), cutaneous inflammation resolved in 24 h. This was demonstrated histologically by clearance of all CD64-expressing macrophages, followed by clearance of other inflammatory cells. Clinical parameters associated with inflammation, such as local skin temperature and vasodilation, also decreased.
Thepen
T
T
Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
van Vuuren
A J
AJ
Kiekens
R C
RC
Damen
C A
CA
Vooijs
W C
WC
van De Winkel
J G
JG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002908:Chronic Disease; D003872:Dermatitis / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D003876:Dermatitis, Atopic / Q000276:immunology / Q000473:pathology; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism / Q000633:toxicity*; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D011961:Receptors, Fc / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology; D012276:Ricin / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D012867:Skin / Q000098:blood supply / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013997:Time Factors; D020298:U937 Cells; D014664:Vasodilation / Q000187:drug effects
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D011961:Receptors, Fc; D017452:Receptors, IgG; D012967:Sodium Dodecyl Sulfate; D007371:Interferon-gamma; D012276:Ricin