PubMed · 7515838
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M W Turner. 1994. Mannose binding protein.. https://doi.org/10.1042/bst0220088
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Lipopolysaccharide-binding protein (LBP), an acute-phase protein recognizing lipopolysaccharide (LPS), catalyzes in low concentrations its transfer to the cellular LPS receptor consisting of CD14 and Toll-like receptor-4. It has recently been shown that high concentrations of recombinant LBP can protect mice in a peritonitis model from the lethal effects of LPS. To determine whether in humans the acute-phase rise of LBP concentrations can inhibit LPS binding to monocytes and induction of proinflammatory cytokines, LBP concentrations were analyzed in 63 patients meeting the American College of Chest Physicians/Society of Critical Care Medicine criteria of severe sepsis or septic shock and the ability of these sera to modulate LPS effects in vitro was assessed employing different assays. Transfer of fluorescein isothiocyanate-labeled LPS to human monocytes was assessed by a fluorescence-activated cell sorter-based method, and activation of monocytes was investigated by measuring LPS-induced tumor necrosis factor-alpha secretion in the presence of the sera. Anti-LBP antibodies and recombinant human LBP were instrumental for depletion and reconstitution of acute-phase sera and subsequent assessment of their modulating effects on LPS activity. Sera of patients with severe sepsis/septic shock exhibited a diminished LPS transfer activity and LPS-induced tumor necrosis factor-alpha secretion as compared with sera from healthy controls. LBP depletion of sepsis sera and addition of rhLBP resulting in concentrations found in severe sepsis confirmed that LBP was the major serum component responsible for the observed effects. In summary, the inhibition of LPS effects by high concentrations of LBP in acute-phase serum, as described here, may represent a novel defense mechanism of the host in severe sepsis and during bacterial infections.
To characterize the serological response in humans to human granulocytic ehrlichiosis (HGE), we prospectively observed 152 patients for as long as 42 months. HGE was confirmed by detection of morulae in blood smears, polymerase chain reaction, blood culture, or a combination of these tests for 94 patients (62.3%), and 92 (97.8%) of the patients had specific serum antibodies thereafter. One hundred twenty-six (99.2%) of 127 patients tested at 1 month were seropositive (89 of 127 patients had seroconversion), and 150 (98.7%) of the 152 patients had become seropositive by 6 months. Eleven patients (7.3%) remained seropositive at 42 months. Neither antibiotic therapy initiated during the first week of illness nor preexisting immunosuppressive conditions abrogated a serological response. Indirect fluorescent antibody testing of acute-phase and convalescent-phase serum samples is a sensitive tool for laboratory confirmation of HGE.
Mammalian myeloid and epithelial cells express several kinds of antibacterial peptides (alpha-/beta-defensins and cathelicidins) that contribute to the innate host defense by killing invading micro-organisms. In this study we evaluated the LPS-neutralizing activities of cathelicidin peptides human CAP18 (cationic antibacterial proteins of 18 kDa) and guinea pig CAP11 using the CD14(+) murine macrophage cell line RAW264.7 and the murine endotoxin shock model. Flow cytometric analysis revealed that CAP18 and CAP11 inhibited the binding of FITC-conjugated LPS to RAW264.7 cells. Likewise, Northern and Western blot analyses indicated that CAP18 and CAP11 suppressed LPS-induced TNF-alpha mRNA and protein expression by RAW264.7 cells. Interestingly, CAP18 and CAP11 possessed LPS-binding activities, and they strongly suppressed the interaction of LPS with LPS binding protein that mediates the transport of LPS to CD14 to facilitate the activation of CD14(+) cells by LPS. Moreover, when CAP18 and CAP11 were preincubated with RAW264.7 cells, they bound to the cell surface CD14 and inhibited the binding of FITC-LPS to the cells. Furthermore, in the murine endotoxin shock model, CAP18 or CAP11 administration inhibited the binding of LPS to CD14(+) cells (peritoneal macrophages) and suppressed LPS-induced TNF-alpha expression by these cells. Together these observations indicate that cathelicidin peptides CAP18 and CAP11 probably exert protective actions against endotoxin shock by blocking the binding of LPS to CD14(+) cells, thereby suppressing the production of cytokines by these cells via their potent binding activities for LPS and CD14.