Expression of L‐Selectin, CD43, and CD44 in Synovial Fluid Neutrophils from Patients with Inflammatory Joint Diseases

Humbría, Alicia; Dı́az-González, Federico; Campanero, Miguel R.; Arroyo, Alicia G.; Laffón, A; González‐Amaro, Roberto; Sánchez-Madrid, Francisco

doi:10.1002/art.1780370307

Cited by 51 publications

(35 citation statements)

References 32 publications

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“…To ascertain the relevance of the above described observations, in vivo experimentation with human healthy volunteers was carried out. A preliminary kinetics study with two individuals taking physiological amounts of indomethacin (25 mg, three times a day, during 4 d), showed a significant neutrophil L-selectin downregulation beginning at 24 h, that was maintained during treatment (data not shown). Therefore, we decided to undertake the study of the neutrophil expression of Lselectin, CD1 lb, and CD la in seven different volunteers 24, and 48 h after starting the administration protocol of indomethacin.…”

Section: Resultsmentioning

confidence: 99%

“…This adhesion molecule is involved in leukocyte-endothelial cell interactions by recognition of carbohydrate determinants found in several endothelial cell ligands, including GlyCAM-l (16), CD34 (17), MAdCAM-1 (18) and P-and E-selectins ( 19). Interestingly, L-selectin is rapidly shed after neutrophil activation both in vitro (20)(21)(22) and in vivo (23,24). A soluble form of L-selectin that retains functional activity has been detected in sera from normal human donors (25).…”

Section: Introductionmentioning

confidence: 99%

“…A soluble form of L-selectin that retains functional activity has been detected in sera from normal human donors (25). In this regard, we have also described a soluble form of L-selectin in synovial fluid from different inflammatory joint diseases (24). Nonsteroidal antiinflammatory drugs (NSAIDs)' are a heterogeneous group of chemical compounds very commonly prescribed for the control of inflammatory human diseases (26).…”

Section: Introductionmentioning

confidence: 99%

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Prevention of in vitro neutrophil-endothelial attachment through shedding of L-selectin by nonsteroidal antiinflammatory drugs.

Dı́az-González¹,

González‐Álvaro²,

Campanero³

et al. 1995

J. Clin. Invest.

154

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The activation of the endothelial cells by extravascular stimuli is the key event in the extravasation of circulating leukocytes to target tissues. L-selectin, a member of the selectin family, is constitutively expressed by white cells, and is the molecule involved in the initial binding of leukocytes to activated endothelium. After activation, leukocytes rapidly release L-selectin from the cell surface, -suggesting that the functional activity of this molecule is controlled in large part by its appearance and disappearance from cell surface. We have studied in a neutrophil-activated endothelial cell binding assay, the effect of different antiinflammatory drugs (steroidal and nonsteroidal) in the L-selectin-mediated interaction of neutrophils with activated endothelial cells. Some nonsteroidal antiinflammatory drugs (NSAIDs), such as indomethacin, diclofenac, ketoprofen, and aspirin, but not steroids, strongly inhibited the neutrophil-endothelial cell attachment. Furthermore, we also investigated the underlying mechanism of this functional effect. The expression of L-selectin on the neutrophil surface rapidly decreased in the presence of different NSAIDs, in a dose-and timedependent manner, whereas no changes in the expression of other adhesion molecules such as CD11a, CD11b, CD31, or ICAM-3 (CD50) were observed. Interestingly, studies in vivo on healthy volunteers treated with physiological doses of indomethacin showed a significant decrease of L-selectin neutrophil expression. Only diclofenac induced an upregulation of CD11b expression, suggesting an activating effect on neutrophils. No enzyme release was observed upon treatment of neutrophils with different NSAIDs, indicating a lack of degranulatory activity of NSAIDs, with the exception of diclofenac. The downregulation of L-selectin expression was due to the rapid cleavage and shedding of the membrane L-selectin, as determined by both immunoprecipitation from "2I-labeled neutrophils, and quantitative estimation in cell-free supernatants. These results suggest that NSAIDs exert a specific action on adhesion receptor expression in neutrophils, which might account, at least in part, for the antiinflammatory activities of NSAIDs. (J. Clin. Invest. 1995.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prevention of in vitro neutrophil-endothelial attachment through shedding of L-selectin by nonsteroidal antiinflammatory drugs.

Dı́az-González¹,

González‐Álvaro²,

Campanero³

et al. 1995

J. Clin. Invest.

154

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“…Antibodies and Reagents-The following monoclonal antibodies (mAbs) were used: Bear-1 anti-CD11b, TP1/40 anti-CD11a, TP1/15 anti-CD31, D3/9 anti-CD45, Mo-2 anti-CD14, and P3X63 myeloma culture supernatant as a negative control (26,27). The Leu-8 anti-Lselectin mAb was purchased from Becton Dickinson Immunocytometry Systems (Mountain View, CA).…”

Section: Methodsmentioning

confidence: 99%

“…Upon activation, L-selectin is enzymatically cleaved from neutrophils cell surface both in vitro (32,33) and in vivo (27,34). Variations in the expression of CD11b and CD45, two glycoproteins contained in the membrane of secretory granules of neutrophils, can be considered as an indirect measurement of neutrophil activation (26,35).…”

Section: Nsaids Can Be Classified In Three Categories According To Thmentioning

confidence: 99%

Structure-Function Relationship and Role of Tumor Necrosis Factor-α-converting Enzyme in the Down-regulation of L-selectin by Non-steroidal Anti-inflammatory Drugs

Gómez-Gaviro¹,

González‐Álvaro²,

Domínguez‐Jiménez³

et al. 2002

Journal of Biological Chemistry

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It has been recently described that some non-steroidal anti-inflammatory drugs (NSAIDs) are able to induce the shedding of L-selectin in neutrophils, an adhesion molecule that plays an essential role in the inflammatory response. We have found that, according to this capability, NSAIDs could be grouped into three categories. A high releaser group (flufenamic, meclofenamic, and mefenamic acids, diclofenac and aceclofenac), a group of moderate releasers (aspirin, indomethacin, nimesulide, flurbiprofen, and ketoprofen), and a nonreleaser group (phenylbutazone and the oxicams, piroxicam and meloxicam). Only NSAIDs from the high releaser group shared diphenylamine in their chemical structure. The amine group of this chemical agent proved to be essential for the anti-L-selectin activity of diphenylamine-based NSAIDs. The presence of a carboxylic acid group in the diphenylamine (N-phenylanthranilic acid) highly increased its ability to reduce the L-selectin surface expression in neutrophils. Diphenylamine and N-phenylanthranilic acid neither affected COX activity in platelets nor modified the activation state of neutrophils. Diphenylamine-related compounds, which include the diphenylamine-based NSAIDs caused a variable reduction in the neutrophil intracellular ATP concentration, which correlated with the differential ability of such compounds to trigger L-selectin shedding (r ‫؍‬ 0.97, p < 0.01). Diphenylaminerelated compounds failed to down-regulate L-selectin in a tumor necrosis factor-␣-converting enzyme (TACE)-deficient murine monocytic cell line. Our data indicate that diphenylamine seems to be the structural core of NSAIDs accounting for their down-regulatory activity of L-selectin leukocyte expression. Diphenylamine and its related compounds exert this action on L-selectin through a prostaglandin-independent, TACE-dependent mechanism that seems to be linked to the capability of these agents to uncouple the mitochondrial oxidative phosphorylation.

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Vascular endothelial growth factor expression by activated synovial leukocytes in rheumatoid arthritis: Critical involvement of the interaction with synovial fibroblasts

Kasama¹,

Shiozawa²,

Kobayashi³

et al. 2001

Arthritis & Rheumatism

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Objective To examine the expression and regulation of the angiogenic factor, vascular endothelial growth factor (VEGF), by fibroblast‐like synoviocytes (FLS), monocytes, and polymorphonuclear neutrophils (PMNs) isolated from the synovial fluid (SF) of rheumatoid arthritis (RA) patients. Methods Monocytes or PMNs obtained from RA SF were cocultured with unstimulated, semiconfluent RA FLS. Culture supernatants were assayed for the proliferation and in vitro tube formation of endothelial cells, and for the production of VEGF, by enzyme‐linked immunosorbent assay. The expression of VEGF messenger RNA and protein was also determined by reverse transcription–polymerase chain reaction and immunohistochemistry, respectively. Results We found that the interaction of inflammatory, activated leukocytes with FLS resulted in synergistic increases in VEGF expression and secretion, which contributed to the proliferation of endothelial cells and to in vitro endothelial tube formation. The induction of VEGF was mediated via specific adhesion molecules, as indicated by the finding that anti‐integrin antibodies significantly inhibited VEGF. Furthermore, the levels of VEGF secretion correlated with the expression of cell surface integrin (CD11b and CD18) on both monocytes and PMNs in the SF. Conclusion VEGF expression within inflamed joints thus appears to be regulated not only by inflammatory cytokines, but also by the physical interaction of activated leukocytes and FLS. Once expressed, VEGF likely plays a crucial role in the neovascularization of the pannus and the progressive joint destruction associated with the synovial inflammation of RA.

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Expression of L‐Selectin, CD43, and CD44 in Synovial Fluid Neutrophils from Patients with Inflammatory Joint Diseases

Cited by 51 publications

References 32 publications

Prevention of in vitro neutrophil-endothelial attachment through shedding of L-selectin by nonsteroidal antiinflammatory drugs.

Prevention of in vitro neutrophil-endothelial attachment through shedding of L-selectin by nonsteroidal antiinflammatory drugs.

Structure-Function Relationship and Role of Tumor Necrosis Factor-α-converting Enzyme in the Down-regulation of L-selectin by Non-steroidal Anti-inflammatory Drugs

Vascular endothelial growth factor expression by activated synovial leukocytes in rheumatoid arthritis: Critical involvement of the interaction with synovial fibroblasts

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