Recombinant bovine soluble CD14 reduces severity of experimental Escherichia coli mastitis in mice.
Endotoxin, or lipopolysaccharide (LPS), is responsible for pathogenesis of infections induced by Gram-negative bacteria, such as E. coli. The cellular response to LPS is modulated by interactions among LPS, LPS-binding protein (LBP) and CD14. Accumulated evidence shows that the soluble form of CD14 (sCD14) competes with membrane-bound CD14 (mCD14) for LPS and plays a pivotal role in regulating bacterial infection and septic shock caused by Gram-negative bacteria. Recombinant bovine sCD14 (rbosCD14) was produced by transfected insect sf/9 cells and its biological function was evaluated in mice. Eighty-one 8-week old BALB/cj female mice were randomly assigned to two groups, and injected intraperitoneally with either LPS (8 microg/g of body weight, n = 41) or LPS plus rbosCD14 (6.8 microg/g of body weight, n = 40). Survival rate at 24 h after injection for mice injected with either LPS or LPS plus rbosCD14 was 30 and 72%, respectively (P < 0.01). At 48 h survival rate was 7 and 37%, respectively (P < 0.01). To investigate the protective effect of rbosCD14 on experimentally induced mastitis in mice, two abdominal contralateral mammary glands of 7 lactating BALB/cj mice were injected through the teat canal with 10-20 colony-forming units (CFU) of Escherichia coli. One gland simultaneously received rbosCD14 (6 microg) and the other saline. At 24 h after challenge, glands that received rbosCD14 had less swelling and hemorrhaging, significantly lower bacterial counts (P < 0.05) and lower concentrations of TNF-alpha (P < 0.05). Results indicate that rbosCD14 is biologically functional and reduces mortality in mice from endotoxin shock and severity of intramammary infection by E. coli.
Lee
Jai-Wei
JW
Department of Animal Science, McGill University, Ste-Anne-de-Bellevue, QC H9X 3V9, Canada.
Paape
Max J
MJ
Zhao
Xin
X
D000818:Animals; D002417:Cattle; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000472:pathogenicity / Q000502:physiology; D004927:Escherichia coli Infections / Q000188:drug therapy*; D005260:Female; D018950:Lipopolysaccharide Receptors / Q000737:chemistry / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000009:adverse effects; D008321:Mammary Glands, Animal / Q000473:pathology; D008413:Mastitis / Q000188:drug therapy* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D012772:Shock, Septic / Q000382:microbiology / Q000517:prevention & control; D012995:Solubility
D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides