title: Differential effects of GM-CSF and G-CSF on infiltration of dendritic cells during early left ventricular remodeling after myocardial infarction.
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 microg/kg/day, MI-G, n = 33), a GM-CSF inducer (romurtide, 200 microg/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-gamma 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.
authors.affiliation: Division of Cardiology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Naito
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Anzai
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sugano
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Maekawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Matsuno
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000276:immunology
chemical_list: D018840:HSP70 Heat-Shock Proteins; C495343:Tlr2 protein, rat; C495347:Tlr4 protein, rat; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D016753:Interleukin-10; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor