PMID- 1390585
OWN - NLM
STAT- MEDLINE
DCOM- 19921125
LR  - 20191028
IS  - 1049-8834 (Print)
IS  - 1049-8834 (Linking)
VI  - 12
IP  - 10
DP  - 1992 Oct
TI  - Redirected targeting of LDL to human monocyte Fc gamma receptors with bispecific 
      antibodies.
PG  - 1131-8
AB  - Recent studies indicate that low density lipoprotein (LDL)-immune complexes 
      consisting of anti-LDL antibodies bound to LDL may contribute to macrophage foam 
      cell development by uptake through immunoglobulin G (IgG) Fc receptors. As human 
      mononuclear phagocytes possess three structurally and functionally distinct 
      classes of IgG Fc receptors, we developed a system whereby the effects of 
      LDL-immune complexes could be studied with respect to each type of IgG Fc 
      receptor. Novel bispecific antibodies consisting of anti-Fc gamma receptor 
      antibodies linked to anti-LDL antibodies were used to prepare bispecific 
      LDL-immune complexes for targeting to specific Fc gamma receptors. In this 
      report, the effects of bispecific LDL-immune complexes directed to Fc gamma 
      receptor types I, II, and III were studied primarily with monocytes and were 
      compared with the effects of similarly prepared bispecific complexes that 
      targeted LDL to human leukocyte antigen (HLA) class I antigens. Each type of 
      bispecific antibody was effective in targeting 125I-LDL to its respective site on 
      the cell surface. Using fluorophore-labeled LDL and flow cytometry, bispecific 
      complexes directed to Fc gamma receptor types I or II but not to HLA class I 
      antigens caused a two- to sevenfold increase in cell-associated fluorescence 
      relative to control cells treated with LDL in the absence of bispecific antibody. 
      Uptake occurred in the presence of excess unlabeled LDL, acetylated LDL, and 
      antioxidants. That the bispecific complexes triggered metabolic uptake was 
      supported by studies of kinetics and temperature dependence. Using 125I-labeled 
      complexes, metabolic degradation of LDL was demonstrated in association with each 
      of the three types of Fc gamma receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Morganelli, P M
AU  - Morganelli PM
AD  - Veterans Administration Hospital, Research Service, White River Junction, VT 
      05009.
FAU - Kitzmiller, T J
AU  - Kitzmiller TJ
FAU - Hemmer, R
AU  - Hemmer R
FAU - Fanger, M W
AU  - Fanger MW
LA  - eng
GR  - AI-19053/AI/NIAID NIH HHS/United States
GR  - CA-44794/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Arterioscler Thromb
JT  - Arteriosclerosis and thrombosis : a journal of vascular biology
JID - 9101388
RN  - 0 (Antibodies)
RN  - 0 (Antigen-Antibody Complex)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Receptors, IgG)
SB  - IM
MH  - Antibodies
MH  - Antigen-Antibody Complex/metabolism
MH  - Arteriosclerosis/*metabolism
MH  - Binding Sites, Antibody
MH  - Foam Cells/*metabolism
MH  - Humans
MH  - Lipoproteins, LDL/*metabolism
MH  - Monocytes/immunology/*metabolism
MH  - Receptors, IgG/immunology/*metabolism
EDAT- 1992/10/01 00:00
MHDA- 1992/10/01 00:01
CRDT- 1992/10/01 00:00
PHST- 1992/10/01 00:00 [pubmed]
PHST- 1992/10/01 00:01 [medline]
PHST- 1992/10/01 00:00 [entrez]
AID - 10.1161/01.atv.12.10.1131 [doi]
PST - ppublish
SO  - Arterioscler Thromb. 1992 Oct;12(10):1131-8. doi: 10.1161/01.atv.12.10.1131.