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The axonal guidance receptor neogenin promotes acute inflammation.

König K, Gatidou D, Granja T, Meier J, Rosenberger P, Mirakaj V - PLoS ONE (2012)

Bottom Line: A crucial target receptor for NGPs during embryonic development is the neogenin receptor, however its role during acute inflammation is unknown.In studies employing bone marrow chimeric animals we found the hematopoietic presence of Neo1(-/-) to be responsible for the attenuated inflammatory response.Taken together our studies suggest that the guidance receptor neogenin holds crucial importance for the propagation of an acute inflammatory response and further define mechanisms shared between the nervous and the immune system.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital, Eberhard-Karls University Tübingen, Tübingen, Germany.

ABSTRACT
Neuronal guidance proteins (NGP) were originally described in the context of axonal growth and migration. Yet recent work has demonstrated that NGPs also serve as guidance cues for immune competent cells. A crucial target receptor for NGPs during embryonic development is the neogenin receptor, however its role during acute inflammation is unknown. We report here that neogenin is abundantly expressed outside the nervous system and that animals with endogenous repression of neogenin (Neo1(-/-)) demonstrate attenuated changes of acute inflammation. Studies using functional inhibition of neogenin resulted in a significant attenuation of inflammatory peritonitis. In studies employing bone marrow chimeric animals we found the hematopoietic presence of Neo1(-/-) to be responsible for the attenuated inflammatory response. Taken together our studies suggest that the guidance receptor neogenin holds crucial importance for the propagation of an acute inflammatory response and further define mechanisms shared between the nervous and the immune system.

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Functional inhibition of neogenin dampens acute inflammatory peritonitis.WT animals were injected i.p. with NaCl or 1 mg of zymosan A (ZyA) and subsequently i.v. with either IgG control or anti-Neogenin (Anti-Neo1) antibody (1 µg) and peritoneal lavage obtained after 8 hours A) Cell count in peritoneal lavage of Neo1−/− and WT animals B) Myeloperoxidase (MPO) activity in peritoneal lavage C) Protein content in peritoneal lavage of Neo1−/− and WT animals D) Representative histological analysis of the peritoneum, the mesenterial fat and cytospin samples of the peritoneal lavage in Neo1−/− and WT animals 8 hours following intraperitoneal NaCl or ZyA injection. Sections prepared with hematoxylin-eosin staining (Magnification ×400, insert ×1000; Data are Mean ± SEM, n = 6 per group, *P<0.05, **P<0.01, ***P<0.001 as indicated).
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pone-0032145-g004: Functional inhibition of neogenin dampens acute inflammatory peritonitis.WT animals were injected i.p. with NaCl or 1 mg of zymosan A (ZyA) and subsequently i.v. with either IgG control or anti-Neogenin (Anti-Neo1) antibody (1 µg) and peritoneal lavage obtained after 8 hours A) Cell count in peritoneal lavage of Neo1−/− and WT animals B) Myeloperoxidase (MPO) activity in peritoneal lavage C) Protein content in peritoneal lavage of Neo1−/− and WT animals D) Representative histological analysis of the peritoneum, the mesenterial fat and cytospin samples of the peritoneal lavage in Neo1−/− and WT animals 8 hours following intraperitoneal NaCl or ZyA injection. Sections prepared with hematoxylin-eosin staining (Magnification ×400, insert ×1000; Data are Mean ± SEM, n = 6 per group, *P<0.05, **P<0.01, ***P<0.001 as indicated).

Mentions: To further define the role of neogenin during acute inflammatory peritonitis we injected WT animals with functionally inhibiting neogenin antibody (anti-Neo1) and appropriate IgG isotype as control. Following this we found a significant reduction of the cell number within the peritoneal fluid of anti-Neo1 injected animals compared to IgG controls (×106, anti-Neo1 1.90±0.13 vs. IgG 3.44±0.3, p<0.01; Figure 4A). This difference between groups was also present when evaluating the MPO activity and the protein content within the peritoneal lavage (Figure 4B and C). The evaluation of histological sections demonstrated significant attenuation of tissue destruction and infiltration of inflammatory cells into the mesenterial fat following anti-Neo1 injection (Figure 4D). To further strengthen this finding we evaluated cytokine levels within the peritoneal lavage and found a reduction of TNF-α (pg/ml, anti-Neo1 17±3 vs. IgG 31±5, p<0.01), IL-1β (pg/ml, anti-Neo1 643±87 vs. IgG 871±51, p<0.05), IL-6 (pg/ml, anti-Neo1 1725±326 vs. IgG 2988±425, p<0.05) and KC (pg/ml, anti-Neo1 1576±406 vs. IgG 3421±851, p<0.05) (Figure 5A–D).


The axonal guidance receptor neogenin promotes acute inflammation.

König K, Gatidou D, Granja T, Meier J, Rosenberger P, Mirakaj V - PLoS ONE (2012)

Functional inhibition of neogenin dampens acute inflammatory peritonitis.WT animals were injected i.p. with NaCl or 1 mg of zymosan A (ZyA) and subsequently i.v. with either IgG control or anti-Neogenin (Anti-Neo1) antibody (1 µg) and peritoneal lavage obtained after 8 hours A) Cell count in peritoneal lavage of Neo1−/− and WT animals B) Myeloperoxidase (MPO) activity in peritoneal lavage C) Protein content in peritoneal lavage of Neo1−/− and WT animals D) Representative histological analysis of the peritoneum, the mesenterial fat and cytospin samples of the peritoneal lavage in Neo1−/− and WT animals 8 hours following intraperitoneal NaCl or ZyA injection. Sections prepared with hematoxylin-eosin staining (Magnification ×400, insert ×1000; Data are Mean ± SEM, n = 6 per group, *P<0.05, **P<0.01, ***P<0.001 as indicated).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3295751&req=5

pone-0032145-g004: Functional inhibition of neogenin dampens acute inflammatory peritonitis.WT animals were injected i.p. with NaCl or 1 mg of zymosan A (ZyA) and subsequently i.v. with either IgG control or anti-Neogenin (Anti-Neo1) antibody (1 µg) and peritoneal lavage obtained after 8 hours A) Cell count in peritoneal lavage of Neo1−/− and WT animals B) Myeloperoxidase (MPO) activity in peritoneal lavage C) Protein content in peritoneal lavage of Neo1−/− and WT animals D) Representative histological analysis of the peritoneum, the mesenterial fat and cytospin samples of the peritoneal lavage in Neo1−/− and WT animals 8 hours following intraperitoneal NaCl or ZyA injection. Sections prepared with hematoxylin-eosin staining (Magnification ×400, insert ×1000; Data are Mean ± SEM, n = 6 per group, *P<0.05, **P<0.01, ***P<0.001 as indicated).
Mentions: To further define the role of neogenin during acute inflammatory peritonitis we injected WT animals with functionally inhibiting neogenin antibody (anti-Neo1) and appropriate IgG isotype as control. Following this we found a significant reduction of the cell number within the peritoneal fluid of anti-Neo1 injected animals compared to IgG controls (×106, anti-Neo1 1.90±0.13 vs. IgG 3.44±0.3, p<0.01; Figure 4A). This difference between groups was also present when evaluating the MPO activity and the protein content within the peritoneal lavage (Figure 4B and C). The evaluation of histological sections demonstrated significant attenuation of tissue destruction and infiltration of inflammatory cells into the mesenterial fat following anti-Neo1 injection (Figure 4D). To further strengthen this finding we evaluated cytokine levels within the peritoneal lavage and found a reduction of TNF-α (pg/ml, anti-Neo1 17±3 vs. IgG 31±5, p<0.01), IL-1β (pg/ml, anti-Neo1 643±87 vs. IgG 871±51, p<0.05), IL-6 (pg/ml, anti-Neo1 1725±326 vs. IgG 2988±425, p<0.05) and KC (pg/ml, anti-Neo1 1576±406 vs. IgG 3421±851, p<0.05) (Figure 5A–D).

Bottom Line: A crucial target receptor for NGPs during embryonic development is the neogenin receptor, however its role during acute inflammation is unknown.In studies employing bone marrow chimeric animals we found the hematopoietic presence of Neo1(-/-) to be responsible for the attenuated inflammatory response.Taken together our studies suggest that the guidance receptor neogenin holds crucial importance for the propagation of an acute inflammatory response and further define mechanisms shared between the nervous and the immune system.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital, Eberhard-Karls University Tübingen, Tübingen, Germany.

ABSTRACT
Neuronal guidance proteins (NGP) were originally described in the context of axonal growth and migration. Yet recent work has demonstrated that NGPs also serve as guidance cues for immune competent cells. A crucial target receptor for NGPs during embryonic development is the neogenin receptor, however its role during acute inflammation is unknown. We report here that neogenin is abundantly expressed outside the nervous system and that animals with endogenous repression of neogenin (Neo1(-/-)) demonstrate attenuated changes of acute inflammation. Studies using functional inhibition of neogenin resulted in a significant attenuation of inflammatory peritonitis. In studies employing bone marrow chimeric animals we found the hematopoietic presence of Neo1(-/-) to be responsible for the attenuated inflammatory response. Taken together our studies suggest that the guidance receptor neogenin holds crucial importance for the propagation of an acute inflammatory response and further define mechanisms shared between the nervous and the immune system.

Show MeSH
Related in: MedlinePlus