Alteration of Mononuclear Cell Immune-Associated Antigen Expression, Interleukin-1 Expression, and Antigen Presentation During Intra-Abdominal Infection

Gallinaro, Robert N.; Naziri, Wade; McMasters, Kelly M.; Peyton, James C.; Cheadle, William G.

doi:10.1097/00024382-199402000-00008

Cited by 14 publications

(9 citation statements)

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“…Thus, it is possible that the impaired costimulatory ability of CD40L-activated monocytes from septic patients was due to reduced surface expression of these molecules. In agreement with these findings, the results of recent studies indicate that the macrophage antigen-presenting capacity appears to become dysfunctional by 24 h after sepsis is induced (3) and remains at subnormal levels for up to 14 days (14). In contrast with the reduced ability to upregulate the expression of CD80 and CD86, CD40L-activated monocytes from septic patients proved able to optimally increase the expression of CD40.…”

Section: Vol 15 2008 Monocytic Cd40l Responses Are Reduced During Ssupporting

confidence: 65%

Downregulation of CD40 Ligand Response in Monocytes from Sepsis Patients

Sinistro

Almerighi

Ciaprini

et al. 2008

Clin Vaccine Immunol

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It has been suggested that a defective adaptive immune response contributes to septic immunosuppression. Here, the response of monocytes to CD40 ligand (CD40L) for patients with sepsis due to infection with gram-negative organisms has been analyzed. Compared to cells from controls, monocytes from septic patients showed significantly reduced production of tumor necrosis factor alpha, interleukin-1␤ (IL-1␤), and IL-12 and were unable to acquire high levels of CD80 and CD86 molecules. These alterations were observed at the onset of sepsis and persisted at day 7. However, the ability of monocytes to respond to CD40L stimulation was partially but significantly restored in cells from patients who recovered from sepsis. In addition, costimulation of autologous CD4؉ T lymphocytes by CD40L-activated monocytes from septic patients failed to induce cell proliferation and gamma interferon production. Finally, the ability of CD40L to rescue monocytes from apoptosis was severely impaired. We conclude that downregulation of the CD40L response may be an appropriate model for the monocyte alteration observed during septic immunosuppression and may help in the development of novel therapeutic strategies.

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Section: Vol 15 2008 Monocytic Cd40l Responses Are Reduced During Ssupporting

confidence: 65%

Downregulation of CD40 Ligand Response in Monocytes from Sepsis Patients

Sinistro

Almerighi

Ciaprini

et al. 2008

Clin Vaccine Immunol

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“…In so doing, they not only serve as a member of the first line of defense against microbial pathogens, but also act as a bridge between activation of the innate and adaptive response to foreign agents [12]. Notably, sepsis studies show that macrophages are important contributors to the pro-inflammatory/innate immune (systemic inflammatory response syndrome; SIRS) response [15, 16], and they show marked evidence of dysfunction/immune suppression/re-programming of key processes associated with pathogen phagocytosis, pro-inflammatory cytokine productive capacity [15, 16] along with the ability to present/ process microbial antigen(s) for presentation to T-cells [16–18]. In this regard, we have recently demonstrated that the negative immunoregulatory cell surface receptor, Programmed Cell Death Receptor-1 (PD-1; CD279), is markedly upregulated on blood monocytes and peritoneal macrophages during sepsis [19].…”

Section: Introductionmentioning

confidence: 99%

Sepsis-Induced Potentiation of Peritoneal Macrophage Migration Is Mitigated by Programmed Cell Death Receptor-1 Gene Deficiency

et al. 2013

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The effect of programmed cell death receptor-1 (PD-1) on phagocyte function has not been extensively described. Here we report that experimental mouse sepsis, cecal ligation and puncture (CLP), induced a marked increase in peritoneal macrophage random migration, motility and cell spread, but these changes were lost in the absence of PD-1. Alternatively, phagocytic activity was inversely affected. In vitro cell culture imaging studies, with the macrophage cell line J774, documented that blocking PD-1 with antibody led to aggregation of the cytoskeletal proteins α-actinin and F-actin. Further experiments looking at ex vivo peritoneal macrophages from mice illustrated that a similar pattern of α-actinin and F-actin was evident on cells from wild-type CLP mice but not PD-1-/- CLP mouse cells. We also observed that fMLP-induced migration by J774 cells was markedly attenuated using PD-1 blocking antibodies, a nonselective phosphatase inhibitor and a selective Ras-related protein 1 inhibitor. Finally, peritoneal macrophages derived from CLP as opposed to Sham mice demonstrated aspects of both cell surface co-localization with CD11b and internalization of PD-1 within vacuoles independent of CD11b staining. Together, we believe the data support a role for PD-1 in mediating aspects of innate macrophage immune dysfunction during sepsis, heretofore unappreciated.

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“…Some aspects of this peritoneal macrophage dysfunction are, however, apparent as early as 1-4 h after the onset of sepsis [10]. If the animal survives, the defect in peritoneal macrophage antigen presentation capability remains at sub-normal levels up to 14 days after the onset of sepsis [11]. Declines in macrophage capacity to release cytokines are also evident in these septic animals [12,13].…”

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confidence: 99%