Concurrent Upregulation of Urokinase Plasminogen Activator Receptor and CD11b during Tuberculosis and Experimental Endotoxemia

Juffermans, Nicole P.; Dekkers, P. E. P.; Verbon, Annelies; Speelman, Peter; Deventer, S. J. H. Van; Poll, Tom van der

doi:10.1128/iai.69.8.5182-5185.2001

Cited by 33 publications

(27 citation statements)

References 14 publications

(8 reference statements)

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“…By doing so we were able to demonstrate increased expression of uPAR on both monocytes and granulocytes at the primary place of infection. These data are in accordance with previous data showing an increased release of uPAR in both plasma and urine of patients with urosepsis (36) and increased uPAR cell surface expression on monocytes of healthy volunteers injected with endotoxin (9,10).…”

Section: Discussionsupporting

confidence: 93%

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Urokinase Receptor Is Necessary for Bacterial Defense against Pneumonia-Derived Septic Melioidosis by Facilitating Phagocytosis

Wiersinga

Kager

Hovius

et al. 2010

The Journal of Immunology

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Urokinase receptor (urokinase-type plasminogen activator receptor [uPAR], CD87), a GPI-anchored protein, is considered to play an important role in inflammation and fibrinolysis. The Gram-negative bacterium Burkholderia pseudomallei is able to survive and replicate within leukocytes and causes melioidosis, an important cause of pneumonia-derived community-acquired sepsis in Southeast Asia. In this study, we investigated the expression and function of uPAR both in patients with septic melioidosis and in a murine model of experimental melioidosis. uPAR mRNA and surface expression was increased in patients with septic melioidosis in/on both peripheral blood monocytes and granulocytes as well as in the pulmonary compartment during experimental pneumonia-derived melioidosis in mice. uPAR-deficient mice intranasally infected with B. pseudomallei showed an enhanced growth and dissemination of B. pseudomallei when compared with wild-type mice, corresponding with increased pulmonary and hepatic inflammation. uPAR knockout mice demonstrated significantly reduced neutrophil migration toward the pulmonary compartment after inoculation with B. pseudomallei. Further in vitro experiments showed that uPAR-deficient macrophages and granulocytes display a markedly impaired phagocytosis of B. pseudomallei. Additional studies showed that uPAR deficiency did not influence hemostatic and fibrinolytic responses during severe melioidosis. These data suggest that uPAR is crucially involved in the host defense against sepsis caused by B. pseudomallei by facilitating the migration of neutrophils toward the primary site of infection and subsequently facilitating the phagocytosis of B. pseudomallei.

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Section: Discussionsupporting

confidence: 93%

“…In humans, i.v. injection of LPS was associated with an upregulation of uPAR on circulating monocytes and granulocytes (9,10). However, the precise role of uPAR in human sepsis is still largely undefined.…”

mentioning

confidence: 99%

Urokinase Receptor Is Necessary for Bacterial Defense against Pneumonia-Derived Septic Melioidosis by Facilitating Phagocytosis

Wiersinga

Kager

Hovius

et al. 2010

The Journal of Immunology

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“…Human endotoxemia has been used previously by other investigators as an experimental model to examine diverse aspects of the inflammatory response including changes in leukocyte antigen expression. [28][29][30] In the present study, we show that changes in nCD64 expression following LPS administration can generally be characterized as biphasic. In examining relationships between hematological changes and nCD64 expression, we found that LPS administration was accompanied by an initial rapid decline in the absolute neutrophil (ANC) and immature granulocyte counts at 1 h, followed by an Fig.…”

Section: Discussionmentioning

confidence: 88%

Hematological indices, inflammatory markers and neutrophil CD64 expression: comparative trends during experimental human endotoxemia

Meer

Pickkers

Scott

et al. 2007

Journal of Endotoxin Research

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CD64 is a high-affinity FcγRI receptor expressed by activated neutrophils that has been recently evaluated as a potential sepsis parameter. In the present study, the kinetics of neutrophil membrane CD64 expression were examined during a standardized inflammatory response, using a human endotoxemia model, and compared with hematological indices, CRP, cytokines and interleukins. Ten healthy subjects received 2 ng/kg intravenous Escherichia coli lipopolysaccharide (LPS). After administration of LPS, neutrophil CD64 showed a biphasic response, characterized by a first increase from 108.5 ± 7.5 to 133 ± 6 AFU after 1 h ( P = 0.047) and a second increase that started at 6 h and reached its maximum of 167 ± 13 AFU at 22 h ( P < 0.0001). CRP concentrations increased to 40 ± 5 mg/dl 22 h after the administration of LPS. The cytokines and interleukins reached their maximum response within 1—2 h. The maximum values of pro-inflammatory cytokines (TNF-α, IFN-γ and IL-6) correlated with the CD64 expression at 22 h after LPS administration ( r2 = 0.76, r2 = 0.78, r2 = 0.81, respectively, all P < 0.05), whereas this correlation was not found for the anti-inflammatory IL-10 ( r2 = 0.058, P = 0.54), suggesting that neutrophil CD64 expression might be a quantitative marker for innate immunity that could easily be used in the clinical setting.

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“…[28][29][30][50][51][52] Phagocytosis and clearance of apoptotic cells are critical to the resolution of inflammation. 1,2 Integrins, especially the integrin ␣ V ␤ 3, are major receptors for PtdSer and play a major role in the clearance of apoptotic cells.…”

mentioning

confidence: 99%

Participation of the urokinase receptor in neutrophil efferocytosis

Park

Liu

Tsuruta

et al. 2009

Blood

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Concurrent Upregulation of Urokinase Plasminogen Activator Receptor and CD11b during Tuberculosis and Experimental Endotoxemia

Cited by 33 publications

References 14 publications

Urokinase Receptor Is Necessary for Bacterial Defense against Pneumonia-Derived Septic Melioidosis by Facilitating Phagocytosis

Urokinase Receptor Is Necessary for Bacterial Defense against Pneumonia-Derived Septic Melioidosis by Facilitating Phagocytosis

Hematological indices, inflammatory markers and neutrophil CD64 expression: comparative trends during experimental human endotoxemia

Participation of the urokinase receptor in neutrophil efferocytosis

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