THE ANTI-LIPID-A MONOCLONAL-ANTIBODY E5 BINDS TO ROUGH GRAM-NEGATIVE BACTERIA, FIXES C3, AND FACILITATES BINDING OF BACTERIAL IMMUNE-COMPLEXES TO BOTH ERYTHROCYTES AND MONOCYTES

Citation
Ma. Seelen et al., THE ANTI-LIPID-A MONOCLONAL-ANTIBODY E5 BINDS TO ROUGH GRAM-NEGATIVE BACTERIA, FIXES C3, AND FACILITATES BINDING OF BACTERIAL IMMUNE-COMPLEXES TO BOTH ERYTHROCYTES AND MONOCYTES, Immunology, 84(4), 1995, pp. 653-661
Citations number
38
Categorie Soggetti
Immunology
Journal title
ISSN journal
00192805
Volume
84
Issue
4
Year of publication
1995
Pages
653 - 661
Database
ISI
SICI code
0019-2805(1995)84:4<653:TAMEBT>2.0.ZU;2-M
Abstract
Treatment of patients with septic shock using monoclonal antibodies (m Abs) to endotoxin is still controversial. Clinical trials of E5, one o f the mAbs directed against the lipid A moiety of lipopolysaccharide ( LPS), are currently in progress, The mechanisms of action of this, and other antibodies under clinical evaluation, are, however, poorly unde rstood. In this study we examined in vitro the ways in which E5 intera cted with Gram-negative bacteria, complement, erythrocytes and monocyt es. By fluorescence-activated cell sorter (FAGS) analysis we showed di rect, dose-dependent binding of E5 to Escherichia coli (E. coli) and S almonella minnesota (S. minnesota). Antibody binding to S. minnesota w as enhanced by treatment with the p-lactam antibiotic amoxycillin, but not by treatment with the aminoglycoside gentamicin. Immune complexes formed between E5 and both species of Gram-negative bacteria activate d both classical and alternative complement pathways, but only in the case of S. minnesota did this facilitate binding to erythrocyte CR1 an d monocyte CR3. Bacterial C3b and iC3b fixation by E5 was quantified u sing specific mAbs. These observations suggest that E5 may enhance bac terial clearance in several ways: (1) by facilitating direct complemen t fixation; (2) by facilitating the binding of opsonized bacteria to c ells of the mononuclear phagocyte system; (3) by enabling bacteria to bind to erythrocyte CRI (CD35), allowing safe carriage in the circulat ion to the fixed macrophages of the liver and spleen; (4) by acting sy nergistically with beta-lactam antibiotics.