Complement receptor 3 (CR3; CD18/CD11b) plays an important role in the recognition and clearance of Streptococcus pneumoniae (pneumococci) by neutrophils. The purpose of the present study was to characterize the modulation of CR3 surface expression on neutrophils exposed to pneumococci and to assess its functional significance. CR3 was detected with fluorescent phytoerythrin-labelled anti-CR3 (CD11b) antibodies, quantified with a fluorescence cell counter (FACS) and localized by confocal fluorescence microscopy. Uptake of fluorescent FITC-labelled pneumococci was quantified by FACS. Whole blood from healthy volunteers was exposed at 37 °C to killed whole type III Streptococcus pneumoniae (KSP; 108/ml) or to a positive control (Escherichia coli lipopolysaccharide) that enhanced CR3 surface expression on neutrophils to a comparable extent. Varying the concentration of KSP between 105 and 108 organisms/ml progressively augmented CR3 surface expression measured at 1 h, whereas the response declined at 109/ml. The diminished response to 109 KSP/ml proved to be time-dependent, with surface CR3 up-regulated maximally within 5 min, and down-regulated thereafter. Labelling of CR3 during exposure demonstrated accelerated receptor sequestration, and confocal fluorescence microscopy demonstrated internalized CR3. Cooling to 16 °C, to inhibit the up-regulation of CR3 surface expression, also inhibited the uptake of FITC-labelled KSP and morphological changes. Accelerated down-regulation of surface CR3 expression by exposure to 109/ml unlabelled KSP diminished the uptake of labelled KSP added subsequently. In contrast, lipopolysaccharide-induced up-regulation of CR3 expression increased the uptake of labelled KSP. Together, these experiments reveal dynamic modulation of CR3 expression on the surface of neutrophils exposed to pneumococci and a functional correlate of this modulation. Thus neutrophil expression of CR3 changes dynamically in response to exposure of neutrophils to progressively higher concentrations of pneumococci, conditions that mimic early neutrophil recruitment to densely infected lung tissue in acute pneumococcal pneumonia.
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Research Article|
June 01 2003
Modulation of neutrophil complement receptor 3 expression by pneumococci
James H. WILLIAMS, JR;
James H. WILLIAMS, JR
*Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Irvine, CA, U.S.A.
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Madeleine V. PAHL;
Madeleine V. PAHL
†Division of Nephrology and Hypertension, Department of Medicine, University of California, Irvine, CA, U.S.A.
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Donna KWONG;
Donna KWONG
*Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Irvine, CA, U.S.A.
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Jeng ZHANG;
Jeng ZHANG
†Division of Nephrology and Hypertension, Department of Medicine, University of California, Irvine, CA, U.S.A.
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Denise HATAKEYAMA;
Denise HATAKEYAMA
*Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Irvine, CA, U.S.A.
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Khawaja AHMAD;
Khawaja AHMAD
*Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Irvine, CA, U.S.A.
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Majid NADERI;
Majid NADERI
*Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Irvine, CA, U.S.A.
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Minh KIM;
Minh KIM
*Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Irvine, CA, U.S.A.
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Nosratola VAZIRI
†Division of Nephrology and Hypertension, Department of Medicine, University of California, Irvine, CA, U.S.A.
Correspondence: Dr N. D. Vaziri, Division of Nephrology and Hypertension, University of California Irvine Medical Center, 101 City Drive South, Bldg 53, Rm 125, Rt 81, Orange, CA 92868, U.S.A. (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
July 08 2002
Revision Received:
January 10 2003
Accepted:
January 27 2003
Accepted Manuscript online:
January 27 2003
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2003 The Biochemical Society
2003
Clin Sci (Lond) (2003) 104 (6): 615–625.
Article history
Received:
July 08 2002
Revision Received:
January 10 2003
Accepted:
January 27 2003
Accepted Manuscript online:
January 27 2003
Citation
James H. WILLIAMS, Madeleine V. PAHL, Donna KWONG, Jeng ZHANG, Denise HATAKEYAMA, Khawaja AHMAD, Majid NADERI, Minh KIM, Nosratola VAZIRI; Modulation of neutrophil complement receptor 3 expression by pneumococci. Clin Sci (Lond) 1 June 2003; 104 (6): 615–625. doi: https://doi.org/10.1042/CS20020176
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