Processing of the Plasmodium chabaudi chabaudi AS merozite surface protein 1 in vivo and in vitro.

Processing of the Plasmodium merozoite surface protein 1 (MSP-1) has been described for parasites maintained under in vitro conditions. We have now demonstrated, using CBA/Ca mice infected with Plasmodium chabaudi chabaudi AS, that MSP-1 processing also occurs in vivo. The major proteolytic cleavage sites and a processing scheme were deduced from N-terminal amino-acid sequences of the MSP-1 breakdown products. Comparison of MSP-1 processing in P. falciparum and P.c. chabaudi indicates a degree of conservation and in two cases the position of protease cleavage appears identical. Significant amounts of MSP-1 polypeptides are found in plasma during schizogony. Various aspects of MSP-1 processing including immunological and physiological reactions in the host during the critical period of schizogony can now be examined in vivo

The response of the innate immune and cardiovascular systems to LPS in pregnant and nonpregnant mice

Sepsis is the leading cause of direct maternal mortality, but there are no data directly comparing the response to sepsis in pregnant and nonpregnant (NP) individuals. This study uses a mouse model of sepsis to test the hypothesis that the cardiovascular response to sepsis is more marked during pregnancy. Female CD1 mice had radiotelemetry probes implanted and were time mated. NP and day 16 pregnant CD-1 mice received intraperitoneal lipopolysaccharide (LPS; 10 μg, serotype 0111: B4). In a separate study, tissue and serum (for RNA, protein and flow cytometry studies), aorta and uterine vessels (for wire myography) were collected after LPS or vehicle control administration. Administration of LPS resulted in a greater fall in blood pressure in pregnant mice compared to NP mice. This occurred with similar changes in the circulating levels of cytokines, vasoactive factors, and circulating leukocytes, but with a greater monocyte and lesser neutrophil margination in the lungs of pregnant mice. Baseline markers of cardiac dysfunction and apoptosis as well as cytokine expression were higher in pregnant mice, but the response to LPS was similar in both groups as was the ex vivo assessment of vascular function. In pregnant mice, nonfatal sepsis is associated with a more marked hypotensive response but not a greater immune response. We conclude that endotoxemia induces a more marked hypotensive response in pregnant compared to NP mice. These changes were not associated with a more marked systemic inflammatory response in pregnant mice, although monocyte lung margination was greater. The more marked hypotensive response to LPS may explain the greater vulnerability to some infections exhibited by pregnant women

Circulating MV levels were elevated in burns patients.

<p>Plasma from healthy volunteers (HV), burns patients on day of admission, and sepsis patients was analyzed by flow cytometry to quantify MVs of different cellular origin: CD45+ leukocyte-derived (<b>A</b>), CD105+ endothelial-derived (<b>B</b>), CD66b+/CD11b+ granulocyte-derived (<b>C</b>), and CD45+/CD14+ monocyte-derived (<b>D</b>). Data are log-transformed and analyzed by one-way ANOVA with Tukey’s tests (<b>A</b>, <b>C</b> and <b>D;</b> mean ± SD) or Kruskal-Wallis with Dunn’s tests (<b>B;</b> median ± interquartile range). *<i>p</i> < 0.05, **<i>p</i> < 0.01, ***<i>p</i> < 0.001.</p

Comparison of circulating MV levels in burns patients on day 0 and day 2.

<p>Plasma from burns patients on admission day 0 and post-admission day 2 was analyzed by flow cytometry to quantify MVs of different cellular origin: CD45+ leukocyte-derived (<b>A</b>), CD105+ endothelia-derived (<b>B</b>), CD66b+/CD11b+ granulocyte-derived (<b>C</b>), and CD45+/CD14+ monocyte-derived (<b>D</b>). Data from individual patients are log-transformed and analyzed by paired t test (<b>A</b>, <b>C</b> and <b>D</b>) or Wilcoxon signed rank test (<b>B</b>). *p < 0.05.</p

Receiver operator characteristic curves for circulating leukocyte MVs in burns patients.

<p>Receiver operating characteristic (ROC) curves and corresponding area under the curve values for: leukocyte-derived MVs, neutrophil-derived MVs and CRP (<b>A</b>), and for BOBI, ABSI and TBSA (<b>B</b>). *<i>p</i> < 0.05, **<i>p</i> < 0.01.</p

Burns patient demographics, assessment scores and outcome, with survivor and non-survivor comparisons.

<p>Burns patient demographics, assessment scores and outcome, with survivor and non-survivor comparisons.</p

Comparison of circulating MV levels in burns and sepsis patient survivors and non-survivors.

<p>Levels of MV subtypes were compared between burns patients that recovered (survivors, n = 10) or died in burns ICU (non-survivors, n = 5) (<b>A</b>) and sepsis patients that recovered (n = 11) or died (n = 4) in the general ICU (<b>B</b>). Data are log-transformed and analyzed by t tests (for burns: leukocyte-, granulocyte- and monocyte-derived MVs; sepsis: leukocyte- and granulocyte-derived MVs; mean ± SD) or Mann-Whitney U tests (for the remainder; median ± interquartile range). Levels of total leukocyte- and granulocyte-derived MVs were higher in burns non-survivors than survivors, **<i>p</i> < 0.01.</p