Differential effects of GM-CSF and G-CSF on infiltration of dendritic cells during early left ventricular remodeling after myocardial infarction

Kotaro Naito, Toshihisa Anzai, Yasuo Sugano, Yuichiro Maekawa, Takashi Kohno, Tsutomu Yoshikawa, Kenjiro Matsuno, Satoshi Ogawa

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Abstract

Several lines of evidence suggest that the immune activation after myocardial infarction (MI) induces secondary myocardial injury. Although dendritic cells (DC) are potent regulators of immunity, their role in MI is still undetermined. We investigated the effect of DC modulation by CSF on left ventricular (LV) remodeling after MI. MI was induced by ligation of the left coronary artery in male Wistar rats. G-CSF (20 μg/kg/day, MI-G, n = 33), a GM-CSF inducer (romurtide, 200 μg/kg/day, MI-GM, n = 28), or saline (MI-C, n = 55) was administered for 7 days. On day 14, MI-G animals had higher LV max dP/dt and smaller LV dimensions, whereas MI-GM animals had lower LV max dP/dt and larger LV dimensions than did MI-C animals, despite similar infarct size. In MI-C, OX62+ DC infiltrated the infarcted and border areas, peaking on day 7. Bromodeoxyuridine-positive DC were observed in the border area during convalescence. Infiltration by DC was decreased in MI-G animals and increased in MI-GM animals compared with MI-C (p < 0.05). In the infarcted area, the heat shock protein 70, TLR2 and TLR4, and IFN-γ expression were reduced in MI-G, but increased in MI-GM in comparison with those in MI-C animals. IL-10 expression was higher in MI-G and lower in MI-GM than in MI-C animals. In conclusion, G-CSF improves and GM-CSF exacerbates early postinfarction LV remodeling in association with modulation of DC infiltration. Suppression of DC-mediated immunity could be a new strategy for the treatment of LV remodeling after MI.

Original languageEnglish
Pages (from-to)5691-5701
Number of pages11
JournalJournal of Immunology
Volume181
Issue number8
Publication statusPublished - 2008

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Ventricular Remodeling
Granulocyte Colony-Stimulating Factor
Granulocyte-Macrophage Colony-Stimulating Factor
Dendritic Cells
Myocardial Infarction

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Naito, K., Anzai, T., Sugano, Y., Maekawa, Y., Kohno, T., Yoshikawa, T., ... Ogawa, S. (2008). Differential effects of GM-CSF and G-CSF on infiltration of dendritic cells during early left ventricular remodeling after myocardial infarction. Journal of Immunology, 181(8), 5691-5701.

Differential effects of GM-CSF and G-CSF on infiltration of dendritic cells during early left ventricular remodeling after myocardial infarction. / Naito, Kotaro; Anzai, Toshihisa; Sugano, Yasuo; Maekawa, Yuichiro; Kohno, Takashi; Yoshikawa, Tsutomu; Matsuno, Kenjiro; Ogawa, Satoshi.

In: Journal of Immunology, Vol. 181, No. 8, 2008, p. 5691-5701.

Research output: Contribution to journalArticle

Naito, K, Anzai, T, Sugano, Y, Maekawa, Y, Kohno, T, Yoshikawa, T, Matsuno, K & Ogawa, S 2008, 'Differential effects of GM-CSF and G-CSF on infiltration of dendritic cells during early left ventricular remodeling after myocardial infarction', Journal of Immunology, vol. 181, no. 8, pp. 5691-5701.
Naito, Kotaro ; Anzai, Toshihisa ; Sugano, Yasuo ; Maekawa, Yuichiro ; Kohno, Takashi ; Yoshikawa, Tsutomu ; Matsuno, Kenjiro ; Ogawa, Satoshi. / Differential effects of GM-CSF and G-CSF on infiltration of dendritic cells during early left ventricular remodeling after myocardial infarction. In: Journal of Immunology. 2008 ; Vol. 181, No. 8. pp. 5691-5701.
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AU - Kohno, Takashi

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AU - Matsuno, Kenjiro

AU - Ogawa, Satoshi

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N2 - Several lines of evidence suggest that the immune activation after myocardial infarction (MI) induces secondary myocardial injury. Although dendritic cells (DC) are potent regulators of immunity, their role in MI is still undetermined. We investigated the effect of DC modulation by CSF on left ventricular (LV) remodeling after MI. MI was induced by ligation of the left coronary artery in male Wistar rats. G-CSF (20 μg/kg/day, MI-G, n = 33), a GM-CSF inducer (romurtide, 200 μg/kg/day, MI-GM, n = 28), or saline (MI-C, n = 55) was administered for 7 days. On day 14, MI-G animals had higher LV max dP/dt and smaller LV dimensions, whereas MI-GM animals had lower LV max dP/dt and larger LV dimensions than did MI-C animals, despite similar infarct size. In MI-C, OX62+ DC infiltrated the infarcted and border areas, peaking on day 7. Bromodeoxyuridine-positive DC were observed in the border area during convalescence. Infiltration by DC was decreased in MI-G animals and increased in MI-GM animals compared with MI-C (p < 0.05). In the infarcted area, the heat shock protein 70, TLR2 and TLR4, and IFN-γ expression were reduced in MI-G, but increased in MI-GM in comparison with those in MI-C animals. IL-10 expression was higher in MI-G and lower in MI-GM than in MI-C animals. In conclusion, G-CSF improves and GM-CSF exacerbates early postinfarction LV remodeling in association with modulation of DC infiltration. Suppression of DC-mediated immunity could be a new strategy for the treatment of LV remodeling after MI.

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