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Intracellular signalling during neutrophil recruitment.

Mócsai A, Walzog B, Lowell CA - Cardiovasc. Res. (2015)

Bottom Line: Those responses are co-ordinated by a number of cell surface receptors and their complex intracellular signal transduction pathways.We will first discuss signalling steps required for sensing extracellular chemoattractants such as chemokines and lipid mediators and the processes (e.g. PI3-kinase pathways) leading to the translation of extracellular chemoattractant gradients to polarized cellular responses.Mechanistic understanding of these pathways provide better understanding of the inflammation process and may point to novel therapeutic strategies for controlling excessive inflammation during infection or tissue damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Semmelweis University School of Medicine, Tűzoltó utca 37-47, 1094 Budapest, Hungary MTA-SE 'Lendület' Inflammation Physiology Research Group of the Hungarian Academy of Sciences and the Semmelweis University, 1094 Budapest, Hungary mocsai.attila@med.semmelweis-univ.hu.

No MeSH data available.


Related in: MedlinePlus

Indirect effect of neutrophil signalling on leucocyte recruitment. At the site of inflammation, neutrophils migrate through the endothelium to the interstitium where they release pro-inflammatory mediators triggering, either directly or through activation of stromal cells, the recruitment of additional neutrophils. β2-integrins are required for the intrinsic capacity of neutrophils to migrate through the vessel wall, whereas Src-family kinases (and likely Syk, PLCγ2 and Vav family members) are critical for the release of pro-inflammatory mediators and hence the generation of the inflammatory environment.
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CVV159F3: Indirect effect of neutrophil signalling on leucocyte recruitment. At the site of inflammation, neutrophils migrate through the endothelium to the interstitium where they release pro-inflammatory mediators triggering, either directly or through activation of stromal cells, the recruitment of additional neutrophils. β2-integrins are required for the intrinsic capacity of neutrophils to migrate through the vessel wall, whereas Src-family kinases (and likely Syk, PLCγ2 and Vav family members) are critical for the release of pro-inflammatory mediators and hence the generation of the inflammatory environment.

Mentions: Besides amplification through LTB4, there are a number of other inflammatory mediators released by neutrophils that promote the recruitment of other neutrophils in an autoamplifying fashion. Neutrophils are rich sources of chemokines,15 many of which (e.g. CXCL1, CXCL2, CXCL8) act on neutrophils themselves. Adoptive transfer of wild-type neutrophils to BLT1-deficient mice was able to restore arthritis development in the K/BxN serum-transfer model, and it also triggered recruitment of BLT1-deficient recipient neutrophils.47 Besides LTB4, IC activation of neutrophils also triggered the release of neutrophil-acting chemokines (e.g. CXCL2) that are also present at the site of autoantibody-induced in vivo inflammation.115 Therefore, neutrophils appear to release neutrophil-attracting inflammatory mediators other than LTB4. A further follow-up study showed that an initial wave of LTB4-driven neutrophil recruitment is followed by additional waves triggered by chemokine release at the site of inflammation.48 Interestingly, this second wave is induced by neutrophils previously recruited to the site of inflammation, either directly by release of the neutrophil-active chemokine CXCL2 from neutrophils themselves or by the release of IL-1β from the recruited neutrophils which triggers release of neutrophil-active chemokines such as CXCL1, CXCL5, or CCL9 from stromal cells and synovial macrophages.48 Therefore, neutrophils amplify their own recruitment in an autocrine manner using a lipid-cytokine-chemokine cascade during autoantibody-induced arthritis (Figure 3). The activation of this cascade further requires additional signals mediated by C5a and Fcγ receptors.119


Intracellular signalling during neutrophil recruitment.

Mócsai A, Walzog B, Lowell CA - Cardiovasc. Res. (2015)

Indirect effect of neutrophil signalling on leucocyte recruitment. At the site of inflammation, neutrophils migrate through the endothelium to the interstitium where they release pro-inflammatory mediators triggering, either directly or through activation of stromal cells, the recruitment of additional neutrophils. β2-integrins are required for the intrinsic capacity of neutrophils to migrate through the vessel wall, whereas Src-family kinases (and likely Syk, PLCγ2 and Vav family members) are critical for the release of pro-inflammatory mediators and hence the generation of the inflammatory environment.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4502828&req=5

CVV159F3: Indirect effect of neutrophil signalling on leucocyte recruitment. At the site of inflammation, neutrophils migrate through the endothelium to the interstitium where they release pro-inflammatory mediators triggering, either directly or through activation of stromal cells, the recruitment of additional neutrophils. β2-integrins are required for the intrinsic capacity of neutrophils to migrate through the vessel wall, whereas Src-family kinases (and likely Syk, PLCγ2 and Vav family members) are critical for the release of pro-inflammatory mediators and hence the generation of the inflammatory environment.
Mentions: Besides amplification through LTB4, there are a number of other inflammatory mediators released by neutrophils that promote the recruitment of other neutrophils in an autoamplifying fashion. Neutrophils are rich sources of chemokines,15 many of which (e.g. CXCL1, CXCL2, CXCL8) act on neutrophils themselves. Adoptive transfer of wild-type neutrophils to BLT1-deficient mice was able to restore arthritis development in the K/BxN serum-transfer model, and it also triggered recruitment of BLT1-deficient recipient neutrophils.47 Besides LTB4, IC activation of neutrophils also triggered the release of neutrophil-acting chemokines (e.g. CXCL2) that are also present at the site of autoantibody-induced in vivo inflammation.115 Therefore, neutrophils appear to release neutrophil-attracting inflammatory mediators other than LTB4. A further follow-up study showed that an initial wave of LTB4-driven neutrophil recruitment is followed by additional waves triggered by chemokine release at the site of inflammation.48 Interestingly, this second wave is induced by neutrophils previously recruited to the site of inflammation, either directly by release of the neutrophil-active chemokine CXCL2 from neutrophils themselves or by the release of IL-1β from the recruited neutrophils which triggers release of neutrophil-active chemokines such as CXCL1, CXCL5, or CCL9 from stromal cells and synovial macrophages.48 Therefore, neutrophils amplify their own recruitment in an autocrine manner using a lipid-cytokine-chemokine cascade during autoantibody-induced arthritis (Figure 3). The activation of this cascade further requires additional signals mediated by C5a and Fcγ receptors.119

Bottom Line: Those responses are co-ordinated by a number of cell surface receptors and their complex intracellular signal transduction pathways.We will first discuss signalling steps required for sensing extracellular chemoattractants such as chemokines and lipid mediators and the processes (e.g. PI3-kinase pathways) leading to the translation of extracellular chemoattractant gradients to polarized cellular responses.Mechanistic understanding of these pathways provide better understanding of the inflammation process and may point to novel therapeutic strategies for controlling excessive inflammation during infection or tissue damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Semmelweis University School of Medicine, Tűzoltó utca 37-47, 1094 Budapest, Hungary MTA-SE 'Lendület' Inflammation Physiology Research Group of the Hungarian Academy of Sciences and the Semmelweis University, 1094 Budapest, Hungary mocsai.attila@med.semmelweis-univ.hu.

No MeSH data available.


Related in: MedlinePlus