Intercellular adhesion molecule 1 and β2 integrins in C1q-stimulated superoxide production by human neutrophils: An example of a general regulatory mechanism governing acute inflammation

Tyagi, Shivraj; Nicholson‐Weller, Anne; Barbashov, Sergei F.; Tas, Sander W.; Klickstein, Lloyd B.

doi:10.1002/1529-0131(200010)43:10<2248::aid-anr12>3.0.co;2-s

Cited by 18 publications

(10 citation statements)

References 48 publications

(44 reference statements)

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“…Immobilized C1q induces PMN to make and release superoxide (47,48). The PMN receptor that mediates this response is not CR1 (48). Others have found that rabbit anticC1qR partially inhibits C1q-mediated superoxide production by PMN (21), a finding we have confirmed using anti-CRT IgY against a peptide of amino acid residues 24 -43 (data not shown).…”

Section: Discussionsupporting

confidence: 65%

“…In equilibrium binding assays, C1q collagen tail binding to purified CRT requires low ionic strength buffer, as does binding to CR1 (40,46); whereas C1q globular domains bind to adjacent sites in recombinant CRT in normal ionic strength buffer (8). Immobilized C1q induces PMN to make and release superoxide (47,48). The PMN receptor that mediates this response is not CR1 (48).…”

Section: Discussionmentioning

confidence: 99%

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Calreticulin Is at the Surface of Circulating Neutrophils and Uses CD59 as an Adaptor Molecule

Ghiran

Klickstein

Nicholson‐Weller

2003

Journal of Biological Chemistry

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Calreticulin, which has been proposed to be a C1q receptor on neutrophils, has neither a transmembrane domain nor a GPI-anchor attachment site and must utilize an adaptor molecule to attach to the plasma membrane. The expression of ecto-calreticulin on purified human neutrophils did not result from contamination by soluble or intracellular calreticulin released during cell fractionation because it was expressed on circulating neutrophils, and the expression did not increase significantly with neutrophil isolation. All neutrophils expressed calreticulin with a unimodal distribution. Treatment of neutrophils with either a cholesterol-binding agent or phosphatidylinositol-specific phospholipase C dramatically decreased ecto-calreticulin expression indicating that the adaptor molecule(s) are located in lipid rafts and have a GPI-anchor. Analysis for the co-expression of specific GPI-anchored proteins and ecto-calreticulin in cells that were deficient in specific GPI-anchored proteins, indicated that ecto-calreticulin was best associated with CD59. Calreticulin reciprocally immunoprecipited with CD59, which provided direct evidence that CD59 is an adaptor for ecto-calreticulin. Immunofluorescence and confocal microscopy demonstrated that ecto-calreticulin co-localized with a fraction of CD59 at the cell surface. Cross-linking ecto-calreticulin with antibodies induced a Ca 2؉ flux, which suggests that ecto-calreticulin is capable of signaling following ligand binding. Ecto-calreticulin has been associated with diverse cellular functions. An appreciation that the adaptors for ecto-calreticulin are GPI-anchored will provide a framework for understanding any common features underlying ecto-calreticulin ligation.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Calreticulin Is at the Surface of Circulating Neutrophils and Uses CD59 as an Adaptor Molecule

Ghiran

Klickstein

Nicholson‐Weller

2003

Journal of Biological Chemistry

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“…MBL binds to a wide array of carbohydrate structures on microbial surfaces and is believed to mediate direct killing via complement activation (4 -9) or by enhancing phagocytosis by acting as an opsonin (10,11). Recently, complement receptor 1 (CR1/CD35) has been defined as the cellular receptor for MBL (12,13), a finding consistent with the structural relatedness of MBL to C1q, which also binds to CR1 (14,15). MBL is associated with three novel MBL-associated serine proteases (MASPs), MASP-1 (16,17), MASP-2 (18), and MASP-3 (19).…”

Section: Annan-binding Lectin (Mbl)mentioning

confidence: 76%

Regulation of the Mannan-Binding Lectin Pathway of Complement on Neisseria gonorrhoeae by C1-Inhibitor and α2-Macroglobulin

Gulati

Sastry

Jensenius

et al. 2002

The Journal of Immunology

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We examined complement activation by Neisseria gonorrhoeae via the mannan-binding lectin (MBL) pathway in normal human serum. Maximal binding of MBL complexed with MBL-associated serine proteases (MASPs) to N. gonorrhoeae was achieved at a concentration of 0.3 μg/ml. Preopsonization with MBL-MASP at concentrations as low as 0.03 μg/ml resulted in ∼60% killing of otherwise fully serum-resistant gonococci. However, MBL-depleted serum (MBLdS) reconstituted with MBL-MASP before incubation with organisms (postopsonization) failed to kill at a 100-fold higher concentration. Preopsonized organisms showed a 1.5-fold increase in C4, a 2.5-fold increase in C3b, and an ∼25-fold increase in factor Bb binding; enhanced C3b and factor Bb binding was classical pathway dependent. Preopsonization of bacteria with a mixture of pure C1-inhibitor and/or α2-macroglobulin added together with MBL-MASP, all at physiologic concentrations before adding MBLdS, totally reversed killing in 10% reconstituted serum. Reconstitution of MBLdS with supraphysiologic (24 μg/ml) concentrations of MBL-MASP partially overcame the effects of inhibitors (57% killing in 10% reconstituted serum). We also examined the effect of sialylation of gonococcal lipooligosaccharide (LOS) on MBL function. Partial sialylation of LOS did not decrease MBL or C4 binding but did decrease C3b binding by 50% and resulted in 80% survival in 10% serum (lacking bacteria-specific Abs) even when sialylated organisms were preopsonized with MBL. Full sialylation of LOS abolished MBL, C4, and C3b binding, resulting in 100% survival. Our studies indicate that MBL does not participate in complement activation on N. gonorrhoeae in the presence of “complete” serum that contains C1-inhibitor and α2-macroglobulin.

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“…In our experiments, we used stimulated neutrophils as the source of superoxide. Granulocytes (neutrophils or eosinophils) that arrive in the focus of allergic inflammation are activated through their cell surface receptors, including their integrins, which transmit signals and activate NADPH oxidase if appropriate inflammatory mediators, such as activated complements, are present in the tissue [42][43][44]. ROS produced by activated granulocytes in turn enhance eosinophil adhesion to VCAM-1 and thus recruit more eosinophils.…”

Section: Discussionmentioning

confidence: 99%

Superoxide activates very late antigen‐4 on an eosinophil cell line and increases cellular binding to vascular cell adhesion molecule‐1

et al. 2003

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The recruitment of eosinophils to the airway is a key event in the pathogenesis of allergy. Very late antigen-4 (VLA-4), an integrin ligand for vascular cell adhesion molecule-1 (VCAM-1), is expressed on eosinophils. VLA-4-mediated adhesion of eosinophils to VCAM-1 may contribute to their selective recruitment to tissues in allergy. Reactive oxygen species (ROS), including nitric oxide (NO), are abundant in the airway of allergic patients, but their role in pathogenesis of allergy is unclear. In this investigation, we studied the effects of ROS on integrin-mediated eosinophil adhesion. Recombinant soluble VCAM-1 and ICAM-1 were used to test the effects of ROS on the integrin-mediated adhesion of an eosinophil cell line. We used phorbol 12-myristate 13-acetate-stimulated neutrophils and hypoxanthine to generate superoxide, NO donors as sources of NO, and a static cell-to-protein adhesion assay to analyze cellular adhesion. Stimulated neutrophils significantly increased eosinophil binding to VCAM-1, which was reversed in the presence of superoxide dismutase. Neutrophils from a chronic granulomatous disease patient lacked this activity in enhancing eosinophil adhesion. Our results suggest that the balance between ROS molecules in different tissue microenvironments may change the integrin-mediated leukocyte adhesion and is likely to be a key factor in leukocyte recruitment in allergic inflammation.

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Intercellular adhesion molecule 1 and β2 integrins in C1q-stimulated superoxide production by human neutrophils: An example of a general regulatory mechanism governing acute inflammation

Cited by 18 publications

References 48 publications

Calreticulin Is at the Surface of Circulating Neutrophils and Uses CD59 as an Adaptor Molecule

Calreticulin Is at the Surface of Circulating Neutrophils and Uses CD59 as an Adaptor Molecule

Regulation of the Mannan-Binding Lectin Pathway of Complement on Neisseria gonorrhoeae by C1-Inhibitor and α2-Macroglobulin

Superoxide activates very late antigen‐4 on an eosinophil cell line and increases cellular binding to vascular cell adhesion molecule‐1

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