Neutrophil adherence to endothelium is enhanced via adenosine A1 receptors and inhibited via adenosine A2 receptors
We have recently demonstrated that human neutrophils (PMN) possess two different classes of adenosine receptors (A1 and A2) that, when occupied, promote chemotaxis and inhibit the generation of reactive oxygen species (e.g., O2- and H2O2), respectively. We have previously demonstrated that adenosine protects endothelial cells (EC) from injury by stimulated neutrophils (PMN) both by diminishing generation of H2O2 and inhibiting adherence of PMN to EC. We therefore determined whether occupancy of A1 or A2 adenosine receptors regulated adherence of PMN to EC. At concentrations similar to those required to inhibit release of O2- by ligation of A2 receptors, both adenosine (IC50 = 56 nM) and 5'N-ethylcarboxamidoadenosine (NECA, IC50 = 8 nM), the most potent A2 agonist, inhibited adherence to EC by stimulated PMN (FMLP, 0.1 microM). In direct contrast, the specific A1 agonists N6-phenylisopropyladenosine and N6-cyclopentyladenosine (CPA) promoted PMN adherence to EC at concentrations of 1-100 nM. To further investigate the mechanisms by which adenosine receptor agonists affected the adherence of stimulated PMN we examined the effect of NECA (A2) and CPA (A1) on the adherence of PMN to fibrinogen (a ligand for the beta 2 integrin CD11b/CD18) and to gelatin. In a dose-dependent manner (IC50 = 2 nM), NECA inhibited the adherence of FMLP-treated PMN to fibrinogen- but not gelatin-coated plates. In contrast, CPA (A1) promoted adherence of stimulated PMN to gelatin-(EC50 = 13 pM) but not fibrinogen-coated plates. Theophylline (10 microM), an adenosine receptor antagonist, reversed the inhibition by NECA (0.3 microM) of stimulated neutrophil adherence to fibrinogen. These observations not only confirm the presence of A1 and A2 receptors on PMN but also suggest two opposing roles for adenosine in inflammation. Occupancy of A1 receptors promotes neutrophil adherence to endothelium and chemotaxis (a proinflammatory role) whereas occupancy of A2 receptors inhibits adherence and generation of toxic oxygen metabolites (an antiinflammatory role).
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
1992 |
|---|---|
| Erschienen: |
1992 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:148 |
|---|---|
| Enthalten in: |
Journal of immunology (Baltimore, Md. : 1950) - 148(1992), 7 vom: 01. Apr., Seite 2201-6 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cronstein, B N [VerfasserIn] |
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| Anmerkungen: |
Date Completed 15.04.1992 Date Revised 16.11.2017 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM013288555 |
|---|
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| 041 | |a eng | ||
| 100 | 1 | |a Cronstein, B N |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Neutrophil adherence to endothelium is enhanced via adenosine A1 receptors and inhibited via adenosine A2 receptors |
| 264 | 1 | |c 1992 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 15.04.1992 | ||
| 500 | |a Date Revised 16.11.2017 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a We have recently demonstrated that human neutrophils (PMN) possess two different classes of adenosine receptors (A1 and A2) that, when occupied, promote chemotaxis and inhibit the generation of reactive oxygen species (e.g., O2- and H2O2), respectively. We have previously demonstrated that adenosine protects endothelial cells (EC) from injury by stimulated neutrophils (PMN) both by diminishing generation of H2O2 and inhibiting adherence of PMN to EC. We therefore determined whether occupancy of A1 or A2 adenosine receptors regulated adherence of PMN to EC. At concentrations similar to those required to inhibit release of O2- by ligation of A2 receptors, both adenosine (IC50 = 56 nM) and 5'N-ethylcarboxamidoadenosine (NECA, IC50 = 8 nM), the most potent A2 agonist, inhibited adherence to EC by stimulated PMN (FMLP, 0.1 microM). In direct contrast, the specific A1 agonists N6-phenylisopropyladenosine and N6-cyclopentyladenosine (CPA) promoted PMN adherence to EC at concentrations of 1-100 nM. To further investigate the mechanisms by which adenosine receptor agonists affected the adherence of stimulated PMN we examined the effect of NECA (A2) and CPA (A1) on the adherence of PMN to fibrinogen (a ligand for the beta 2 integrin CD11b/CD18) and to gelatin. In a dose-dependent manner (IC50 = 2 nM), NECA inhibited the adherence of FMLP-treated PMN to fibrinogen- but not gelatin-coated plates. In contrast, CPA (A1) promoted adherence of stimulated PMN to gelatin-(EC50 = 13 pM) but not fibrinogen-coated plates. Theophylline (10 microM), an adenosine receptor antagonist, reversed the inhibition by NECA (0.3 microM) of stimulated neutrophil adherence to fibrinogen. These observations not only confirm the presence of A1 and A2 receptors on PMN but also suggest two opposing roles for adenosine in inflammation. Occupancy of A1 receptors promotes neutrophil adherence to endothelium and chemotaxis (a proinflammatory role) whereas occupancy of A2 receptors inhibits adherence and generation of toxic oxygen metabolites (an antiinflammatory role) | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, P.H.S. | |
| 650 | 7 | |a Antigens, CD |2 NLM | |
| 650 | 7 | |a CD18 Antigens |2 NLM | |
| 650 | 7 | |a Macrophage-1 Antigen |2 NLM | |
| 650 | 7 | |a Receptors, Purinergic |2 NLM | |
| 650 | 7 | |a Phenylisopropyladenosine |2 NLM | |
| 650 | 7 | |a 29193-86-0 |2 NLM | |
| 650 | 7 | |a Adenosine-5'-(N-ethylcarboxamide) |2 NLM | |
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| 650 | 7 | |a N(6)-cyclopentyladenosine |2 NLM | |
| 650 | 7 | |a 41552-82-3 |2 NLM | |
| 650 | 7 | |a N-Formylmethionine Leucyl-Phenylalanine |2 NLM | |
| 650 | 7 | |a 59880-97-6 |2 NLM | |
| 650 | 7 | |a Theophylline |2 NLM | |
| 650 | 7 | |a C137DTR5RG |2 NLM | |
| 650 | 7 | |a Adenosine |2 NLM | |
| 650 | 7 | |a K72T3FS567 |2 NLM | |
| 700 | 1 | |a Levin, R I |e verfasserin |4 aut | |
| 700 | 1 | |a Philips, M |e verfasserin |4 aut | |
| 700 | 1 | |a Hirschhorn, R |e verfasserin |4 aut | |
| 700 | 1 | |a Abramson, S B |e verfasserin |4 aut | |
| 700 | 1 | |a Weissmann, G |e verfasserin |4 aut | |
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| 773 | 1 | 8 | |g volume:148 |g year:1992 |g number:7 |g day:01 |g month:04 |g pages:2201-6 |
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