Osteopontin functions as an opsonin and facilitates phagocytosis by macrophages of hydroxyapatite-coated microspheres: Implications for bone wound healing

Pedraza, Claudio E.; Nikolcheva, Liliya G.; Kaartinen, Mari T.; Barralet, Jake E.; McKee, Marc D.

doi:10.1016/j.bone.2008.06.010

Cited by 48 publications

(42 citation statements)

References 46 publications

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“…However, this possibility has been suggested using OPN-coated latex beads, which are internalized more efficiently than are BSA-coated beads (26). We demonstrate that OPN specifically binds to and mediates phagocytosis of bacteria.…”

Section: Discussionmentioning

confidence: 75%

“…Therefore, to ensure that the uptake was also mediated by OPN, we confirmed our data using OPN-coated beads. Whereas CD44 seems to be responsible for macrophage migration (16,49), it does not appear to be a receptor for phagocytosis of OPN-coated beads (26). This suggested that OPN has a hitherto unrecognized receptor for phagocytosis.…”

Section: Discussionmentioning

confidence: 99%

“…Carboxylate-modified fluorescent latex beads (Sigma-Aldrich) were coated with OPN, BSA, or IgG1 essentially as described by Pedraza et al (26). Briefly, 25 l (1.4 ϫ 10 8 ) of beads was transferred to silicone-coated Eppendorf tubes and washed in an appropriate buffer.…”

Section: Protein Coating Of Fluorescent Latex Beadsmentioning

confidence: 99%

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Osteopontin Enhances Phagocytosis through a Novel Osteopontin Receptor, the αXβ2 Integrin

Schack¹,

Stapulionis

Christensen³

et al. 2009

The Journal of Immunology

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Osteopontin (OPN) is a cytokine with multiple functions, including immune defense mechanisms against invading microorganisms. OPN-deficient mice are impaired in clearing intracellular pathogens, suggesting an important role of OPN during phagocytosis, but it remains to be defined how OPN may enhance this innate immune process. Here, we demonstrate that OPN binds to monocytes, but not resting T cells, NK cells, or B cells, and mediates chemoattraction of IL-1-activated human monocytes. Moreover, OPN binds in a specific manner to all known serotypes of the two bacterial species Streptococcus agalactiae and Staphylococcus aureus and opsonizes these bacteria for phagocytosis. We identify the integrin αXβ2 (CD11c/CD18), which is highly expressed on the cell surface of monocytes, as a novel OPN receptor. To eliminate the contribution from other molecular interactions between the bacteria and the phagocyte, we show that OPN-coated synthetic beads are phagocytosed in an αXβ2 integrin-dependent manner. The ligand recognition does not involve the RGD motif previously reported to support binding of OPN to integrins. Taken together, these data identify the αXβ2 integrin as a novel OPN receptor that is required for OPN-mediated phagocytosis, thereby elucidating an important mechanism of an innate immune function of OPN.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

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Osteopontin Enhances Phagocytosis through a Novel Osteopontin Receptor, the αXβ2 Integrin

Schack¹,

Stapulionis

Christensen³

et al. 2009

The Journal of Immunology

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“…Leibovich and Ross (31) reported that elimination of local macrophages at the wound site impairs the wound-healing process, and impaired macrophage phagocytic function also leads to a defect in wound healing (54). Furthermore, macrophages might be activated at the wound site, where a large amount of the intracellular content is released into the extracellular space (29), and these macrophages produce cytokines, growth factors, and chemokines, which promote further recruitment of immune cells (7,41). These tissue macrophages may play important roles in wound healing immediately after surgery.…”

Section: Discussionmentioning

confidence: 99%

Propofol inhibits pressure-stimulated macrophage phagocytosis via the GABA_A receptor and dysregulation of p130cas phosphorylation

Shiratsuchi

Kouatli

et al. 2009

American Journal of Physiology-Cell Physiology

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Surgical stress and anesthesia result in systemic immunosuppression. Propofol, a commonly used anesthetic agent, alters immune cell functions. Previously, we demonstrated that extracellular pressure increases macrophage phagocytosis. We hypothesized that propofol might influence pressure-induced macrophage phagocytosis in monocytes from patients undergoing surgery. Pressure (20 mmHg above ambient pressure) augmented phagocytosis in monocytes from non-propofol-anesthetized patients but reduced phagocytosis in monocytes from propofol-anesthetized patients. In vitro, propofol stimulated phagocytosis but reversed pressure-induced phagocytosis in THP-1 macrophages and monocytes from healthy volunteers. The GABAA receptor antagonists picrotoxin and SR-95531 did not affect basal THP-1 phagocytosis or prevent pressure-stimulated phagocytosis. However, picrotoxin and SR-95531 negated the inhibitory effect of pressure in propofol-treated cells without altering propofol-induced phagocytosis. Phosphorylation of the adaptor protein p130cas was inversely related to phagocytosis: it was inhibited by pressure or propofol but increased by pressure + propofol compared with propofol alone. Reduction of p130cas by small interfering RNA in THP-1 macrophages increased basal phagocytosis and prevented pressure and propofol effects. In conclusion, propofol may alter macrophage responses to pressure via the GABAA receptor and p130cas, whereas pressure also acts via p130cas but independently of GABAA receptors. p130cas may be an important target for modulation of macrophage function in anesthetized patients.

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“…Several studies have shown that the absence of the tissue-remodelling enzyme, MMP9, following injury delays endochondral ossification and alters healing [37,38]. Similarly, the absence of osteopontin, encoded by SPP1 and believed to facilitate the uptake of mineralized matrix [39], causes altered tissue remodelling in mice and, consequently, reduced biomechanical properties [40]. Regulation of macrophage phenotype observed in this study was attributed predominantly to direct interactions between macrophages and the scaffolds, as only modest effects of scaffold-released soluble factors on macrophage activation were observed.…”

Section: Discussionmentioning

confidence: 99%

In vitroresponse of macrophages to ceramic scaffolds used for bone regeneration

Graney

Roohani‐Esfahani

Zreiqat

et al. 2016

J. R. Soc. Interface.

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Macrophages, the primary cells of the inflammatory response, are major regulators of healing, and mediate both bone fracture healing and the inflammatory response to implanted biomaterials. However, their phenotypic contributions to biomaterial-mediated bone repair are incompletely understood. Therefore, we used gene expression and protein secretion analysis to investigate the interactions in vitro between primary human monocytederived macrophages and ceramic scaffolds that have been shown to have varying degrees of success in promoting bone regeneration in vivo. Specifically, baghdadite (Ca 3 ZrSi 2 O 9 ) and strontium-hardystonite-gahnite (Sr-Ca 2 ZnSi 2 O 7 -ZnAl 2 O 4 ) scaffolds were chosen as two materials that enhanced bone regeneration in vivo in large defects under load compared with clinically used tricalcium phosphate-hydroxyapatite (TCP-HA). Principal component analysis revealed that the scaffolds differentially regulated macrophage phenotype. Temporal changes in gene expression included shifts in markers of pro-inflammatory M1, anti-inflammatory M2a and pro-remodelling M2c macrophage phenotypes. Of note, TCP-HA scaffolds promoted upregulation of many M1-related genes and downregulation of many M2a-and M2c-related genes. Effects of the scaffolds on macrophages were attributed primarily to direct cell-scaffold interactions because of only minor changes observed in transwell culture. Ultimately, elucidating macrophage-biomaterial interactions will facilitate the design of immunomodulatory biomaterials for bone repair.

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Osteopontin functions as an opsonin and facilitates phagocytosis by macrophages of hydroxyapatite-coated microspheres: Implications for bone wound healing

Cited by 48 publications

References 46 publications

Osteopontin Enhances Phagocytosis through a Novel Osteopontin Receptor, the αXβ2 Integrin

Osteopontin Enhances Phagocytosis through a Novel Osteopontin Receptor, the αXβ2 Integrin

Propofol inhibits pressure-stimulated macrophage phagocytosis via the GABA_A receptor and dysregulation of p130cas phosphorylation

In vitroresponse of macrophages to ceramic scaffolds used for bone regeneration

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Osteopontin functions as an opsonin and facilitates phagocytosis by macrophages of hydroxyapatite-coated microspheres: Implications for bone wound healing

Cited by 48 publications

References 46 publications

Osteopontin Enhances Phagocytosis through a Novel Osteopontin Receptor, the αXβ2 Integrin

Osteopontin Enhances Phagocytosis through a Novel Osteopontin Receptor, the αXβ2 Integrin

Propofol inhibits pressure-stimulated macrophage phagocytosis via the GABAA receptor and dysregulation of p130cas phosphorylation

In vitroresponse of macrophages to ceramic scaffolds used for bone regeneration

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Propofol inhibits pressure-stimulated macrophage phagocytosis via the GABA_A receptor and dysregulation of p130cas phosphorylation