Resistance of Transgenic Mice Expressing Human Group II Phospholipase A2 to Escherichia coliInfection

ABSTRACT Group II phospholipase A2 (PLA2) is a newly recognized antibacterial acute-phase protein. Recently we observed that transgenic mice expressing group II PLA2 (PLA2+ mice) were able to resist experimental Staphylococcus aureusinfection by killing the bacteria, as indicated by improved survival and by the small numbers of live bacteria in their tissues (V. J. O. Laine, D. S. Grass, and T. J. Nevalainen, J. Immunol. 162:7402–7408, 1999). To establish the role of group II PLA2 in Escherichia coli infection, the host responses of PLA2+ mice and their PLA2-deficient C57BL/6J littermates (PLA2− mice) were studied after intraperitoneal administration of E. coli. The levels of group II PLA2 in sera of PLA2+ mice increased after the administration ofE. coli, and the concentration of group II PLA2 correlated significantly with the catalytic activity of PLA2 in serum. PLA2+ mice showed lower rates of mortality and less bacterial growth in peritoneal lavage fluid, blood, and spleen and liver tissues than PLA2− mice. Unlike the observations with staphylococcal infection, serum and peritoneal lavage fluid did not inhibit the growth of E. coli in vitro. The results indicate that expression of the group II PLA2 transgene improves the host defense of mice against E. coliinfection.

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Role of Myeloid Tet Methylcytosine Dioxygenase 2 in Pulmonary and Peritoneal Inflammation Induced by Lipopolysaccharide and Peritonitis Induced by Escherichia coli

Cells ◽

10.3390/cells11010082 ◽

2021 ◽

Vol 11 (1) ◽

pp. 82

Author(s):

Wanhai Qin ◽

Xanthe Brands ◽

Hisatake Matsumoto ◽

Joe M. Butler ◽

Cornelis van’t Veer ◽

...

Keyword(s):

Peritoneal Lavage ◽

Lavage Fluid ◽

Peritoneal Macrophages ◽

Histone Deacetylation ◽

Peritoneal Lavage Fluid ◽

E Coli ◽

Peritoneal Inflammation ◽

Enhanced Production

Tet methylcytosine dioxygenase 2 (Tet2) mediates demethylation of DNA. We here sought to determine the expression and function of Tet2 in macrophages upon exposure to lipopolysaccharide (LPS), and in the host response to LPS induced lung and peritoneal inflammation, and during Escherichia (E.) coli induced peritonitis. LPS induced Tet2 expression in mouse macrophages and human monocytes in vitro, as well as in human alveolar macrophages after bronchial instillation in vivo. Bone marrow-derived macrophages from myeloid Tet2 deficient (Tet2fl/flLysMCre) mice displayed enhanced production of IL-1β, IL-6 and CXCL1 upon stimulation with several Toll-like receptor agonists; similar results were obtained with LPS stimulated alveolar and peritoneal macrophages. Histone deacetylation was involved in the effect of Tet2 on IL-6 production, whilst methylation at the Il6 promoter was not altered by Tet2 deficiency. Tet2fl/flLysMCre mice showed higher IL-6 and TNF levels in bronchoalveolar and peritoneal lavage fluid after intranasal and intraperitoneal LPS administration, respectively, whilst other inflammatory responses were unaltered. E. coli induced stronger production of IL-1β and IL-6 by Tet2 deficient peritoneal macrophages but not in peritoneal lavage fluid of Tet2fl/flLysMCre mice after in vivo intraperitoneal infection. Tet2fl/flLysMCre mice displayed enhanced bacterial growth during E. coli peritonitis, which was associated with a reduced capacity of Tet2fl/flLysMCre peritoneal macrophages to inhibit the growth of E. coli in vitro. Collectively, these data suggest that Tet2 is involved in the regulation of macrophage functions triggered by LPS and during E. coli infection.

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RESISTANCE OF TRANSGENIC MICE EXPRESSING HUMAN GROUP II PHOSPHOLIPASE A2 TO E. COLI INFECTION

Shock ◽

10.1097/00024382-199703001-00095 ◽

1997 ◽

Vol 7 (Supplement) ◽

pp. 24 ◽

Cited By ~ 1

Author(s):

V JO Laine ◽

T J Nevalainen ◽

D S Grass

Keyword(s):

Transgenic Mice ◽

Phospholipase A2 ◽

Human Group ◽

E Coli ◽

Group Ii

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Extracellular phospholipase A2 activity in cell free peritoneal lavage fluid from mice with zymosan peritonitis

Agents and Actions ◽

10.1007/bf01972817 ◽

1989 ◽

Vol 27 (3-4) ◽

pp. 341-343 ◽

Cited By ~ 12

Author(s):

K. R. Gans ◽

S. R. Lundy ◽

R. L. Dowling ◽

T. M. Stevens ◽

J. S. Kerr

Keyword(s):

Phospholipase A2 ◽

Peritoneal Lavage ◽

Lavage Fluid ◽

Peritoneal Lavage Fluid ◽

Phospholipase A2 Activity ◽

Zymosan Peritonitis

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Role and Regulation of Adipokines during Zymosan-Induced Peritoneal Inflammation in Mice

Endocrinology ◽

10.1210/en.2008-0327 ◽

2008 ◽

Vol 149 (8) ◽

pp. 4080-4085 ◽

Cited By ~ 20

Author(s):

Maria Pini ◽

Melissa E. Gove ◽

Joseph A. Sennello ◽

Jantine W. P. M. van Baal ◽

Lawrence Chan ◽

...

Keyword(s):

Inflammatory Infiltrate ◽

Peritoneal Lavage ◽

Lavage Fluid ◽

Wild Type ◽

Cellular Infiltrate ◽

Peritoneal Lavage Fluid ◽

Peritoneal Inflammation ◽

Leptin Deficiency ◽

Cytokine Levels

Adipokines, cytokines mainly produced by adipocytes, are active participants in the regulation of inflammation. Administration of zymosan (ZY) was used to investigate the regulation and role of adipokines during peritonitis in mice. Injection of ZY led to a significant increase in leptin levels in both serum and peritoneal lavage fluid, whereas a differential trend in local vs. systemic levels was observed for both resistin and adiponectin. The role of leptin in ZY-induced peritonitis was investigated using leptin-deficient ob/ob mice, with and without reconstitution with exogenous leptin. Leptin deficiency was associated with delayed resolution of peritoneal inflammation induced by ZY, because ob/ob mice had a more pronounced cellular infiltrate in the peritoneum as well as higher and prolonged local and systemic levels of IL-6, TNFα, IL-10, and chemokine (C-X-C motif) ligand 2 compared with wild-type mice. Reconstitution with exogenous leptin exacerbated the inflammatory infiltrate and systemic IL-6 levels in ob/ob mice while inhibiting production of TNFα, IL-10, and chemokine (C-X-C motif) ligand 2. In contrast with the important role of leptin in regulating each aspect of ZY-induced peritonitis, adiponectin deficiency was associated only with a decreased inflammatory infiltrate, without affecting cytokine levels. These findings point to a complex role for adipokines in ZY-induced peritonitis and further emphasize the interplay between obesity and inflammation.

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Monoclonal antibodies specific to a Ca2+-bound form of lipocortin I distinguish its Ca2+-dependent phospholipid-binding ability from its ability to inhibit phospholipase A2

Biochemical Journal ◽

10.1042/bj2690709 ◽

1990 ◽

Vol 269 (3) ◽

pp. 709-715 ◽

Cited By ~ 11

Author(s):

H Hayashi ◽

M K Owada ◽

S Sonobe ◽

K Domae ◽

T Yamanouchi ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Phospholipase A2 ◽

Inhibitory Activity ◽

Biological Effects ◽

Free Form ◽

E Coli ◽

Phospholipid Binding ◽

Ef Hand

Lipocortin I, a Ca2(+)-and phospholipid-binding protein without EF-hand structures, has many biological effects in vitro. Its actual role in vivo, however is unknown. We obtained and characterized five monoclonal antibodies to lipocortin I. Two of these monoclonal antibodies (L2 and L4-MAbs) reacted with the Ca(+)-bound form of lipocortin I, but not with the Ca2(+)-free form, both in vivo and in vitro. Lipocortin I required greater than or equal to 10 microM-Ca2+ to bind the two antibodies, and this Ca2+ requirement was not affected by phosphatidylserine. L2-MAb abolished the phospholipase A2 inhibitory activity of lipocortin I and inhibited its binding to Escherichia coli membranes and to phosphatidylserine in vitro. L4-MAb abolished the phospholipase A2 inhibitory activity of lipocortin I, but did not affect its binding to E. coli membranes or to phosphatidylserine. These findings indicated that the inhibition of phospholipase A2 by lipocortin I was not simply due to removal or capping of the substrates in E. coli membranes. Furthermore, an immunofluorescence study using L2-MAb showed the actual existence of Ca2(+)-bound form of lipocortin I in vivo.

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