Biomedical subjects

Sandrine Florquin

Publications and source records attributed to Sandrine Florquin.

99 records · Page 6Linked to original sources

PubMed2002

IL-18 improves the early antimicrobial host response to pneumococcal pneumonia.

To determine the role of endogenous IL-18 during pneumonia, IL-18 gene-deficient (IL-18(-/-)) mice and wild-type (WT) mice were intranasally inoculated with Streptococcus pneumoniae, the most common causative agent of community-acquired pneumonia. Infection with S. pneumoniae increased the expression of IL-18 mRNA and was associated with elevated concentrations of both precursor and mature IL-18 protein within the lungs. IL-18(-/-) mice had significantly more bacteria in their lungs and were more susceptible for progressing to systemic infection at 24 and 48 h postinoculation. Similarly, treatment of WT mice with anti-IL-18 was associated with enhanced outgrowth of pneumococci. In contrast, the clearance of pneumococci from lungs of IL-12(-/-) mice was unaltered when compared with WT mice. Furthermore, anti-IL-12 did not influence bacterial clearance in either IL-18(-/-) or WT mice. These data suggest that endogenous IL-18, but not IL-12, plays an important role in the early antibacterial host response during pneumococcal pneumonia.

Animals↗

PubMed2002

CD44 expression in IgA nephropathy.

Immunoglobulin A (IgA) nephropathy is a frequent, chronic renal disease characterized by a broad spectrum of clinical presentations and pathologic findings. CD44, a family of type I transmembrane glycoproteins involved in cell-cell and cell-matrix interactions, may orchestrate partially the cascade of inflammation, accumulation of myofibroblasts, and fibrosis leading to end-stage renal disease. To clarify the possible role of CD44 in the progression of IgA nephropathy, the expression of CD44 in glomeruli and the tubulointerstitial compartment was analyzed in 25 renal biopsy specimens of patients with IgA nephropathy and was correlated to histopathologic, serologic, and urinary parameters. The expression of CD44 correlated significantly with the degree of glomerular and interstitial damage, even better than the accumulation of alpha-smooth muscle actin-positive myofibroblasts, which is recognized as a reliable marker for the progression of IgA nephropathy. A positive correlation also was found between proteinuria and the expression of CD44 in the tubulointerstitial compartment. The glomerular and tubulointerstitial expression of CD44 correlated with the degree of renal damage in IgA nephropathy and could be a reliable marker of the progression of IgA nephropathy. CD44 may have a pivotal role in the cascade of renal inflammation and fibrosis.

Adult↗

PubMed2002

CpG oligodeoxynucleotides enhance host defense during murine tuberculosis.

Oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs activate immune cells to produce cytokines. CpG ODNs protect mice against infections with intracellular bacteria by the induction of a T helper 1 (Th1) response. To determine the effect of CpG ODNs in pulmonary tuberculosis, mice were treated with CpG ODNs or control ODNs at the time of intranasal infection. CpG ODNs reduced mycobacterial outgrowth for up to 5 weeks after Mycobacterium tuberculosis infection and were associated with a decrease in inflammation in lung tissue. CpG treatment was also associated with elevated levels of gamma interferon (IFN-gamma) and decreased levels of interleukin 4 in the lungs and an increased capacity of splenocytes to secrete Th1-type cytokines. CpG ODNs given 2 weeks after infection were still able to reduce mycobacterial outgrowth and to enhance a Th1 response 5 weeks postinfection. Administration of CpG ODNs to IFN-gamma-gene-deficient mice failed to reduce mycobacterial outgrowth. These data suggest that CpG ODNs improve host defense during pulmonary tuberculosis by an IFN-gamma-dependent mechanism.

Adjuvants, Immunologic↗

PubMed2002

Role of interleukin-1 in the pulmonary immune response during Pseudomonas aeruginosa pneumonia.

Pneumonia is associated with elevated concentrations of the proinflammatory cytokine interleukin (IL)-1 in the pulmonary compartment. To study the role of IL-1 in the pathogenesis of Pseudomonas pneumonia, IL-1 receptor type 1 gene-deficient (IL-1R -/-) mice and wild-type mice were intranasally inoculated with Pseudomonas aeruginosa. The absence of the IL-1 signal attenuated the outgrowth of Pseudomonas in lungs, as reflected by an increasing number of colony-forming units (cfu) during Pseudomonas pneumonia in wild-type mice and a concurrently decreasing number of cfu during pulmonary infection in IL-1R -/- mice (P < 0.05, IL-1R -/- mice vs. wild-type mice). Influx of neutrophils was decreased in bronchoalveolar lavage fluids in IL-1R -/- mice compared with wild-type mice. Similarly, lung levels of cytokines (tumor necrosis factor-alpha, IL-6) and chemokines (macrophage inflammatory protein-2 and KC) were lower in IL-1R -/- mice 24 h postinoculation. Consistent with results obtained in IL-1R -/- mice, treatment of wild-type mice with IL-1R antagonist also diminished outgrowth of Pseudomonas when compared with wild-type mice treated with vehicle (P < 0.05). These results demonstrate that an absence or reduction in endogenous IL-1 activity improves host defense against Pseudomonas pneumonia while suppressing the inflammatory response.

Animals↗

PubMed2001

The role of interferon-gamma in murine pneumococcal pneumonia.

To determine the role of interferon (IFN)-gamma in pneumonia, IFN-gamma receptor-deficient (IFN-gamma R(-/-)) and 129/Sv (wild-type [wt]) mice were inoculated intranasally with Streptococcus pneumoniae. Although mortality did not differ between the groups 48 h after inoculation, IFN-gamma R(-/-) mice had significantly fewer pneumococci in their lungs than the wt mice. Similarly, IFN-gamma(-/-) mice had fewer colony-forming units in lungs than wt mice. The relatively increased resistance of IFN-gamma R(-/-) mice was not related to favorable effects on defense mechanisms known to contribute to antibacterial immunity-that is, the neutrophilic influx was reduced and the cytokine and nitric oxide levels were similar or lower in IFN-gamma R(-/-) mice. In contrast, mice treated with anti-IFN-gamma did not demonstrate a consistently altered bacterial outgrowth, compared with mice treated with a control antibody. These data suggest that endogenous IFN-gamma, despite its protective role in defense against intracellular pathogens, does not serve a protective role during pneumococcal pneumonia.

Animals↗

PubMed2001

Roles of interleukin-6 and macrophage inflammatory protein-2 in pneumolysin-induced lung inflammation in mice.

Pneumolysin (PLY), a toxin synthesized by Streptococcus pneumoniae, is an important virulence factor in pneumococcal disease. This study evaluated the effects of PLY in lungs of mice. Intranasal inoculation with PLY was associated with a dose-dependent influx of polymorphonuclear leukocytes (PMNL) in bronchoalveolar lavage fluid (BALF) and increased concentrations of interleukin (IL)-6, macrophage inflammatory protein (MIP)-2, and KC in BALF. PLY mutants with either reduced cytolytic activity or reduced cytolytic and complement-activating activities were less potent in inducing PMNL recruitment to the lung (P<.05), which suggests that PLY cytolytic activity is very important for the inflammatory response. IL-6 and MIP-2 also played a role in PLY-induced PMNL recruitment; this response was partially diminished in IL-6 gene-deficient mice and in mice treated with anti-MIP-2 antiserum. PLY may play an important role in the induction of an inflammatory response in the pulmonary compartment in the early phase of pneumococcal pneumonia.

Animals↗

PubMed2001

Impairment of host defence by exotoxin A in Pseudomonas aeruginosa pneumonia in mice.

Exotoxin A (P-ExA) is considered to be a major virulence factor of Pseudomonas aeruginosa. Neutrophils, cytokines and nitric oxide (NO) have been implicated as important components of an effective host defence against bacterial respiratory tract infection. To study the role of P-ExA in the pathogenesis of P. aeruginosa pneumonia, C57Bl/6 mice were inoculated intranasally with wild-type PA103 or a mutant P. aeruginosa strain that did not produce P-ExA, PA103-29. P-ExA facilitated the outgrowth of P. aeruginosa in lungs, as reflected by an increasing number of cfu during pneumonia with strain PA103, whereas the number of cfu decreased during pulmonary infection with strain PA103-29. Influx of neutrophils was similar in broncho-alveolar lavage fluids (BALF) during pneumonia with strains PA103 and PA103-29. Lung levels of cytokines (tumor necrosis factor-alpha, interleukin-6) and chemokines (macrophage inflammatory protein-2, KC) were higher in mice inoculated with strain PA103, whereas BALF concentrations of NO were similar in mice treated with strains PA103 and PA103-29. These data suggest that P-ExA impairs host defence during pneumonia caused by P. aeruginosa by a mechanism that does not involve effects on neutrophil influx, cytokines, chemokines or NO formation.

ADP Ribose Transferases↗

PubMedDate not supplied

Blood cell-derived tissue factor influences host response during murine endotoxemia.

During endotoxemia, blood coagulation becomes activated due to tissue factor (TF) expression on leukocytes and/or endothelial cells. We investigated the influence of blood cell-derived tissue factor on murine endotoxemia. Therefore, we generated mice that lack tissue factor on their blood cells by transplanting tissue factor-deficient hematopoietic stem cells into lethally irradiated wild-type recipients. Control mice were also irradiated but were injected with stem cells from wild-type littermate embryos. Seven weeks after transplantation, the mice received 250 microg of endotoxin intraperitoneally. Three hours later, the mice were bled and plasma and organs were collected to assess inflammation, coagulation, and apoptosis. Mice that lack tissue factor on their blood cells still reacted to endotoxemia, but markedly less than wild-type controls. Blood cell-derived tissue factor-deficient mice showed significantly less clinical symptoms than control mice. Levels of circulating inflammatory mediators and thrombin-antithrombin (TAT) complexes were lower in blood cell-derived tissue factor-deficient mice than in controls. Surprisingly, inflammation was seen more often in blood cell-derived tissue factor-deficient mice than in control mice, but signs of apoptosis were more pronounced in controls. In summary, our data clearly indicate that endotoxin-induced coagulation and inflammation are strongly influenced by blood cell-derived tissue factor.

Animals↗

PubMedDate not supplied

Interleukin-1 receptor antagonist transiently impairs antibacterial defense but not survival in murine pneumococcal pneumonia.

The inhibition of the biological activity of IL-1 by recombinant human IL-1 receptor antagonist (IL-1ra) has been investigated in several, controlled clinical trials. Encouraging results have been reported, in particular in patients with rheumatoid arthritis. In the present study, we investigated the influence of treatment of wild type mice with IL-1ra, which resulted in an incomplete and transient inhibition of IL-1 activity. Treatment with recombinant human IL-1ra resulted in an enhanced bacterial outgrowth in the lungs of BALB/c and C57BL/6 mice early after induction of pneumococcal pneumonia, without influencing survival or the pulmonary inflammatory response. The effect of IL-1ra on the host response to S. pneumoniae pneumonia is modest and transient. The present data, together with the findings in IL-1R*/* mice in earlier work, suggest that IL-1 occupies a role in the pulmonary immune response to S. pneumoniae that is substantially less prominent than that of TNF-alpha.

Animals↗