Monocyte C1-inhibitor synthesis in patients with C1-inhibitor deficiency.
Monocytes of seven out of eight patients with type 1 C1-inhibitor (C1-inh) deficiency (HAE) produced 40% as much C1-inh as monocytes from normal donors (controls). In contrast, monocytes from three patients with type 2 and three patients with acquired C1-inh deficiency produced similar amounts of C1-inh as controls. Recombinant gamma-interferon (gamma-interferon 10 ng/ml) stimulated C1-inh production of C1-inh (eight-10-fold) by control and patients' monocytes. Monocytes from patients with type 1 HAE contained 40% the level of C1-inh messenger ribonucleic acid (mRNA) found in control monocytes. Gamma-interferon increased the abundance of C1-inh mRNA by the same extent in both control and patients' monocytes. C1-inh protein and mRNA were undetectable in the monocytes of one patient, unless stimulated by gamma-interferon. Under these conditions, his monocytes produced comparable amounts of C1-inh (protein and mRNA) as gamma-interferon-stimulated monocytes of the other type 1 HAE patients. The data suggest that in most type 2 HAE patients there is a lesion in the C1-inh gene such that mRNA is transcribed by a single allele.
Lappin
D F
DF
University of Glasgow Pathology Department, Western Infirmary, Scotland, U.K.
McPhaden
A R
AR
Yap
P L
PL
Carter
P E
PE
Birnie
G D
GD
Fothergill
J E
JE
Whaley
K
K
D000799:Angioedema / Q000235:genetics / Q000276:immunology*; D015152:Blotting, Northern; D003174:Complement C1 Inactivator Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D003175:Complement C2 / Q000096:biosynthesis / Q000235:genetics; D004247:DNA / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D009000:Monocytes / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis
D003174:Complement C1 Inactivator Proteins; D003175:Complement C2; D012333:RNA, Messenger; D004247:DNA