Dexamethasone promotes phagocytosis and bacterial killing by human monocytes/macrophages in vitro

Goes, A. van der; Hoekstra, K.; Berg, Timo K. van den; Dijkstra, Christine D.

doi:10.1002/jlb.67.6.801

Cited by 80 publications

(66 citation statements)

References 35 publications

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“…Many forms of beneficial interactions between dexamethasone and leukocytes, promoting less valve destruction (26) as observed in the present study, have been described for bacterial endocarditis. There are in vitro studies which also support the finding that dexamethasone promotes phagocytosis by human monocytes, not only of S. aureus, but of other macromolecules as well, and thereby may contribute to tissue repair after immune-mediated tissue damage or infection (29,30).…”

Section: Discussionmentioning

confidence: 63%

Dexamethasone as Adjuvant Therapy to Moxifloxacin Attenuates Valve Destruction in Experimental Aortic Valve Endocarditis Due to Staphylococcus aureus

Skiadas

Pefanis

Papalois

et al. 2007

Antimicrob Agents Chemother

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Although the beneficial effects of dexamethasone have frequently been investigated in various serious-infection settings, insufficient data on valve histology and cardiac function for infective endocarditis are available. The efficacy of moxifloxacin for the treatment of experimental aortic valve endocarditis due to methicillin-susceptible Staphylococcus aureus and the long-term effects of dexamethasone were evaluated in the current study. Sixty-eight rabbits were randomly assigned to four groups: A, B, C, and D. Group A consisted of 18 animals and functioned as a control group. Groups B and C consisted of 11 and 23 subjects, respectively, which received moxifloxacin for 5 days in a human-like pharmacokinetic simulation. Group D consisted of 16 animals that were administered moxifloxacin plus dexamethasone (0.25 mg/kg of body weight twice a day intravenously). The group B animals were sacrificed a day after the completion of treatment, and group C and D animals were sacrificed after 12 days in order to monitor any possible relapse and allow microbiological, histopathological, and echocardiographic evaluation of the longterm effects of glucocorticoids. No differences in survival, sterilization rates, or inflammatory infiltration and calcification of valve tissue were observed among the treated groups. However, the degrees of valve damage and collagenization were significantly worse, the fibroblast content was higher, and fractional shortening of the left ventricle fluctuated significantly in group C compared to group D (all groups, P < 0.05). We concluded that dexamethasone treatment for experimental S. aureus endocarditis attenuates valve destruction and preserves overall cardiac function without impeding the efficacy of moxifloxacin.

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Section: Discussionmentioning

confidence: 63%

Dexamethasone as Adjuvant Therapy to Moxifloxacin Attenuates Valve Destruction in Experimental Aortic Valve Endocarditis Due to Staphylococcus aureus

Skiadas

Pefanis

Papalois

et al. 2007

Antimicrob Agents Chemother

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“…This suggests that leptin itself may enhance leukotriene synthesis independent of the potential effect of elevated glucocorticoids in the leptin-deficient mouse. It is also important to note that defective alveolar macrophage phagocytosis of bacteria observed in the leptin-deficient mice cannot be explained by excess glucocorticoids, because dexamethasone pretreatment has been shown to enhance macrophage phagocytosis and killing of bacteria in vitro (51). Therefore, the most likely explanation for the host defense impairments against K. pneumoniae in leptin-deficient mice was due to the absence of leptin itself.…”

Section: Discussionmentioning

confidence: 98%

Leptin-Deficient Mice Exhibit Impaired Host Defense in Gram-Negative Pneumonia

Mancuso

Gottschalk

Phare

et al. 2002

The Journal of Immunology

312

266

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Leptin is an adipocyte-derived hormone that is secreted in correlation with total body lipid stores. Serum leptin levels are lowered by the loss of body fat mass that would accompany starvation and malnutrition. Recently, leptin has been shown to modulate innate immune responses such as macrophage phagocytosis and cytokine synthesis in vitro. To determine whether leptin plays a role in the innate host response against Gram-negative pneumonia in vivo, we compared the responses of leptin-deficient and wild-type mice following an intratracheal challenge of Klebsiella pneumoniae. Following K. pneumoniae administration, we observed increased leptin levels in serum, bronchoalveolar lavage fluid, and whole lung homogenates. In a survival study, leptin-deficient mice, as compared with wild-type mice, exhibited increased mortality following K. pneumoniae administration. The increased susceptibility to K. pneumoniae in the leptin-deficient mice was associated with reduced bacterial clearance and defective alveolar macrophage phagocytosis in vitro. The exogenous addition of very high levels of leptin (500 ng/ml) restored the defect in alveolar macrophage phagocytosis of K. pneumoniae in vitro. While there were no differences between wild-type and leptin-deficient mice in lung homogenate cytokines TNF-α, IL-12, or macrophage-inflammatory protein-2 after K. pneumoniae administration, leukotriene synthesis in lung macrophages from leptin-deficient mice was reduced. Leukotriene production was restored by the addition of exogenous leptin (500 ng/ml) to macrophages in vitro. This study demonstrates for the first time that leptin-deficient mice display impaired host defense in bacterial pneumonia that may be due to a defect in alveolar macrophage phagocytosis and leukotriene synthesis.

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“…One possibility is that other p130Cas-like adapters such as HEF1 and Efts/Sin (Ref. 32 and references therein), present in macrophages, may allow the recruitment of Rac/Crk/DOCK180 specifically to membranes in a manner that facilitates phagocytosis of apoptotic cells and possibly other particles (43). Indeed, in preliminary experiments using low density IgG-opsonized particles, we have found that DX-treated monocytes/macrophages are more efficient phagocytes (untreated, 24.5% phagocytosis; DX treated, 53.5% phagocytosis, n ϭ 4).…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid Augmentation of Macrophage Capacity for Phagocytosis of Apoptotic Cells Is Associated with Reduced p130Cas Expression, Loss of Paxillin/pyk2 Phosphorylation, and High Levels of Active Rac

Giles

Ross

Rossi

et al. 2001

The Journal of Immunology

156

122

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Phagocytic clearance of apoptotic granulocytes has a pivotal role in determining an inflammatory outcome, resolution or progression to a chronic state associated with development of fibrotic repair mechanisms, and/or autoimmune responses. In this study, we describe reprogramming of monocyte to macrophage differentiation by glucocorticoids, resulting in a marked augmentation of their capacity for phagocytosis of apoptotic neutrophils. This monocyte/macrophage phenotype was characterized by decreased phosphorylation, and therefore recruitment of paxillin and pyk2 to focal contacts and a down-regulation of p130Cas, a key adaptor molecule in integrin adhesion signaling. Glucocorticoid-treated cells also displayed higher levels of active Rac and cytoskeletal activity, which were mirrored by increases in phagocytic capability for apoptotic neutrophils. We propose that changes in the capacity for reorganization of cytoskeletal elements induced by glucocorticoids are essential for efficient phagocytic uptake of apoptotic cells.

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Dexamethasone promotes phagocytosis and bacterial killing by human monocytes/macrophages in vitro

Cited by 80 publications

References 35 publications

Dexamethasone as Adjuvant Therapy to Moxifloxacin Attenuates Valve Destruction in Experimental Aortic Valve Endocarditis Due to Staphylococcus aureus

Dexamethasone as Adjuvant Therapy to Moxifloxacin Attenuates Valve Destruction in Experimental Aortic Valve Endocarditis Due to Staphylococcus aureus

Leptin-Deficient Mice Exhibit Impaired Host Defense in Gram-Negative Pneumonia

Glucocorticoid Augmentation of Macrophage Capacity for Phagocytosis of Apoptotic Cells Is Associated with Reduced p130Cas Expression, Loss of Paxillin/pyk2 Phosphorylation, and High Levels of Active Rac

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