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1974 ; 54
(2
): 339-48
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Studies on the in vivo effects of antibody Interaction of IgM antibody and
complement in the immune clearance and destruction of erythrocytes in man
#MMPMID4847248
Atkinson JP
; Frank MM
J Clin Invest
1974[Aug]; 54
(2
): 339-48
PMID4847248
show ga
Purified human IgM isoagglutinins were utilized to sensitize (51)Cr-labeled
erythrocytes so as to produce a known number of complement-fixing sites. These
cells were then reinfused into the erythrocyte donor. A minimum of 20 C1-fixing
sites/erythrocyte were required for decreased survival. As the amount of antibody
coating the erythrocytes was increased, a larger percentage was sequestered. With
80 C1-fixing sites, more than 75% of the injected erythrocytes were removed from
the circulation within 10 min. In each case, the clearance pattern consisted of
rapid hepatic sequestration followed by a gradual return of a portion of the
erythrocytes into the circulation where they survived normally. Clearance was
shown to be dependent upon activation of the classical complement pathway, since
sensitized cells survived normally in hereditary angioedema patients with low
levels of C4 and no detectable C2. Exposure of sensitized cells to fresh serum
for 15 min led to the deposition of 550-800 C3 molecules/C1-fixing site. Such
cells were immune adherence positive, were agglutinated by anti-C3b, formed
rosettes with human alveolar macrophages, and were sequestered in vivo,
presumably because of the interaction of cell-bound C3b with the C3b receptor on
hepatic macrophages. After exposure to heated serum as a source of the C3b
inactivator, the cells were immune adherence negative, were agglutinated only by
anti-C3d, did not form rosettes with macrophages, and survived normally in vivo
despite, being Coombs positive. Cleavage of cell-bound C3b to C3d may explain the
release phase of the IgM clearance pattern. Whereas erythrocytes coated with IgM
antibody and complement were previously thought to be sequestered in the liver
because of extensive membrane damage, these experiments suggest that clearance is
determined by the interaction of erythrocyte-bound complement fragments with
specific receptors on hepatic macrophages.