Failure of neutrophil migration toward infectious focus in severe sepsis: a critical event for the outcome of this syndrome

Alves‐Filho, José C.; Benjamim, Cláudia F.; Tavares‐Murta, Beatriz Martins; Cunha, Fernando Q.

doi:10.1590/s0074-02762005000900038

Cited by 45 publications

(28 citation statements)

References 22 publications

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“…In fact, reduction of these parameters is observed in mice submitted to SS induced by perforation of the ligated cecum (6). The process is prevented by pretreatment of the animals with iNOS inhibitors or by the use of iNOS Ϫ/Ϫ mice (22), and increases in neutrophil rolling/adhesion and in the expression of the adhesion molecules can be observed in both situations, whereas NO donors decrease these effects (23,24). Both authentic AGP and natural purified AGP reduced neutrophil migration, rolling, and adhesion of leukocytes to the endothelium of the mesenteric microcirculation of rats also by an NO-dependent mechanism.…”

Section: Discussionmentioning

confidence: 99%

Acute-phase protein α-1-acid glycoprotein mediates neutrophil migration failure in sepsis by a nitric oxide-dependent mechanism

Mestriner¹,

Spiller²,

Laure

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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The reduction of circulating neutrophil migration to infection sites is associated with a poor outcome of severe sepsis. ␣-1-Acid glycoprotein (AGP) was isolated from the sera of severely septic patients by HPLC and acrylamide gel electrophoresis and identified by mass spectrometry. Both the isolated protein and commercial AGP inhibited carrageenin-induced neutrophil migration into the rat peritoneal cavity when administered i.v. at a dose of 4.0 g per rat (95 pmol per rat). Analysis by intravital microscopy demonstrated that both proteins inhibited the rolling and adhesion of leukocytes in the mesenteric microcirculation. The inhibitory activity was blocked by 50 mg/kg aminoguanidine, s.c., and was not demonstrable in inducible nitric oxide synthase (iNOS) knockout mice. Incubation of AGP with neutrophils from healthy subjects induced the production of NO and inhibited the neutrophil chemotaxis by an iNOS/NO/cyclic guanosine 3,5-monophosphatedependent pathway. In addition, AGP induced the L-selectin shedding by neutrophils. The administration of AGP to rats with mild cecal ligation puncture sepsis inhibited neutrophil migration and reduced 7-day survival from Ϸ80% to 20%. These data demonstrate that AGP, an acute-phase protein, inhibits neutrophil migration by an NO-dependent process and suggest that AGP also participates in human sepsis.

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Section: Discussionmentioning

confidence: 99%

Acute-phase protein α-1-acid glycoprotein mediates neutrophil migration failure in sepsis by a nitric oxide-dependent mechanism

Mestriner¹,

Spiller²,

Laure

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…Based on the results of Alves-Filho et al (2006) [3], a comment should be made regarding the inflammatory events during lethal polymicrobial sepsis (infection by two or more different types of bacteria) [2]. They induced lethal polymicrobial sepsis by caecal ligation and puncture (CLP) in wild type and TLR-4 deficient mice and describe that in wild type mice, there is a clear PMN migration failure to the infectious focus compared to the TLR-4 deficient mice.…”

Section: Possible Drawbacks Of the Therapymentioning

confidence: 99%

The toll-like receptor-4 (TLR-4) pathway and its possible role in the pathogenesis ofEscherichia colimastitis in dairy cattle

et al. 2007

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-Mastitis is one of the most costly production diseases in the dairy industry that is caused by a wide array of microorganisms. In this review, we focus on the Gram-negative Escherichia coli infections that often occur at periods when the innate immune defence mechanisms are impaired (i.e., parturition through the first 60 days of lactation). There is substantial evidence demonstrating that at these periods, the expected influx of polymorphonuclear neutrophil leukocytes (PMN) into the mammary gland is delayed during inflammation after intramammary infection with E. coli. Here, we provide some hypotheses on the potential mechanisms of action on how the disease may develop under circumstances of immunosuppression, and describe the potential involvement of the toll-like receptor-4 signal transduction pathway in the pathogenesis of E. coli mastitis. In addition, some ideas are proposed to help prevent E. coli mastitis and potentially other diseases caused by Gram-negative infections in general.

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“…In addition, neutrophils also release cytokines and chemokines, which enhance their own recruitment and activation as well as inducing the migration of other immune cells (2). Our previous studies showed that lethal sepsis induced by cecal ligation and puncture (CLP) 3 or Staphylococcus aureus inoculation is associated with reduction of neutrophil rolling, adhesion, and transmigration to sites of infection (3)(4)(5)(6)(7)(8). The impairment of neutrophil migration was also associated with high mortality and increased numbers of bacteria in peritoneal exudates and blood.…”

mentioning

confidence: 99%

“…The impairment of neutrophil migration was also associated with high mortality and increased numbers of bacteria in peritoneal exudates and blood. Conversely, in nonlethal sepsis, the bacterial infection was restricted to the peritoneal cavity, and neutrophil rolling, adhesion, and migration were not affected, and no significant mortality was observed (3)(4)(5)(6)(7)(8). The mechanism involved in the paralysis of neutrophil migration function is still elusive.…”

mentioning

confidence: 99%

IL-12, but Not IL-18, Is Critical to Neutrophil Activation and Resistance to Polymicrobial Sepsis Induced by Cecal Ligation and Puncture

Moreno¹,

Alves‐Filho²,

Alfaya³

et al. 2006

The Journal of Immunology

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Sepsis is a systemic inflammatory response resulting from local infection due, at least in part, to impaired neutrophil migration. IL-12 and IL-18 play an important role in neutrophil migration. We have investigated the mechanism and relative role of IL-12 and IL-18 in polymicrobial sepsis induced by cecal ligation and puncture (CLP) in mice. Wild-type (WT) and IL-18−/− mice were resistant to sublethal CLP (SL-CLP) sepsis. In contrast, IL-12−/− mice were susceptible to SL-CLP sepsis with high bacteria load in peritoneal cavity and systemic inflammation (serum TNF-α and lung neutrophil infiltration). The magnitude of these events was similar to those observed in WT mice with lethal CLP sepsis. The inability of IL-12−/− mice to restrict the infection was not due to impairment of neutrophil migration, but correlated with decrease of phagocytosis, NO production, and microbicidal activities of their neutrophils, and with reduction of systemic IFN-γ synthesis. Consistent with this observation, IFN-γ−/− mice were as susceptible to SL-CLP as IL-12−/− mice. Moreover, addition of IFN-γ to cultures of neutrophils from IL-12−/− mice restored their phagocytic, microbicidal activities and NO production. Mortality of IL-12−/− mice to SL-CLP was prevented by treatment with IFN-γ. Thus we show that IL-12, but not IL-18, is critical to an efficient host defense in polymicrobial sepsis. IL-12 acts through induction of IFN-γ and stimulation of phagocytic and microbicidal activities of neutrophils, rather than neutrophil migration per se. Our data therefore provide further insight into the defense mechanism against this critical area of infectious disease.

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Failure of neutrophil migration toward infectious focus in severe sepsis: a critical event for the outcome of this syndrome

Cited by 45 publications

References 22 publications

Acute-phase protein α-1-acid glycoprotein mediates neutrophil migration failure in sepsis by a nitric oxide-dependent mechanism

Acute-phase protein α-1-acid glycoprotein mediates neutrophil migration failure in sepsis by a nitric oxide-dependent mechanism

The toll-like receptor-4 (TLR-4) pathway and its possible role in the pathogenesis ofEscherichia colimastitis in dairy cattle

IL-12, but Not IL-18, Is Critical to Neutrophil Activation and Resistance to Polymicrobial Sepsis Induced by Cecal Ligation and Puncture

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