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Nitric oxide produc...
Nitric oxide produced in response to engagement of beta 2 integrins on human neutrophils activates the monomeric GTPases Rap1 and Rap2 and promotes adhesion
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Jenei, Veronika (author)
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Deevi, Ravi Kiran (author)
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Adams, Catherine Anne (author)
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- Axelsson, Lena (author)
- Lund University,Lunds universitet,Experimentell patologi, Malmö,Forskargrupper vid Lunds universitet,Experimental Pathology, Malmö,Lund University Research Groups
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Hirst, David Graham (author)
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- Andersson, Tommy (author)
- Lund University,Lunds universitet,Experimentell patologi, Malmö,Forskargrupper vid Lunds universitet,Experimental Pathology, Malmö,Lund University Research Groups
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- Dib, Karim (author)
- Lund University,Lunds universitet,Experimentell patologi, Malmö,Forskargrupper vid Lunds universitet,Experimental Pathology, Malmö,Lund University Research Groups
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(creator_code:org_t)
- 2006
- 2006
- English.
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In: Journal of Biological Chemistry. - 1083-351X. ; 281:46, s. 35008-35020
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http://dx.doi.org/10... (free)
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Abstract
Subject headings
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- We found that engagement of beta 2 integrins on human neutrophils increased the levels of GTP-bound Rap1 and Rap2. Also, the activation of Rap1 was blocked by PP1, SU6656, LY294002, GF109203X, or BAPTA-AM, which indicates that the downstream signaling events in Rap1 activation involve Src tyrosine kinases, phosphoinositide 3-kinase, protein kinase C, and release of calcium. Surprisingly, the beta 2 integrin-induced activation of Rap2 was not regulated by any of the signaling pathways mentioned above. However, we identified nitric oxide as the signaling molecule involved in beta 2 integrin-induced activation of Rap1 and Rap2. This was illustrated by the fact that engagement of beta 2 integrins increased the production of nitrite, a stable end-product of nitric oxide. Furthermore, pretreatment of neutrophils with N-omega-mono-methy1-L-arginine, or 1400W, which are inhibitors of inducible nitric- oxide synthase, blocked beta 2 integrin-induced activation of Rap1 and Rap2. Similarly, R-P-8pCPT-cGMPS, an inhibitor of cGMP-dependent serine/threonine kinases, also blunted the beta 2 integrin-induced activation of Rap GTPases. Also nitric oxide production and its downstream activation of cGMP-dependent serine/threonine kinases were essential for proper neutrophil adhesion by beta 2 integrins. Thus, we made the novel findings that beta 2 integrin engagement on human neutrophils triggers production of nitric oxide and its downstream signaling is essential for activation of Rap GTPases and neutrophil adhesion.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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