Macrophage CD74 contributes to MIF-induced pulmonary inflammation

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Macrophage CD74 contributes to MIF-induced pulmonary inflammation. / Takahashi, Koichiro; Koga, Kiyokazu; Linge, Helena; Zhang, Yinzhong; Lin, Xinchun; Metz, Christine N; Al-Abed, Yousef; Ojamaa, Kaie; Miller, Edmund J.

In: Respiratory Research, Vol. 10, 33, 04.05.2009.

Research output: Contribution to journalArticle

Harvard

Takahashi, K, Koga, K, Linge, H, Zhang, Y, Lin, X, Metz, CN, Al-Abed, Y, Ojamaa, K & Miller, EJ 2009, 'Macrophage CD74 contributes to MIF-induced pulmonary inflammation', Respiratory Research, vol. 10, 33. https://doi.org/10.1186/1465-9921-10-33

APA

Takahashi, K., Koga, K., Linge, H., Zhang, Y., Lin, X., Metz, C. N., Al-Abed, Y., Ojamaa, K., & Miller, E. J. (2009). Macrophage CD74 contributes to MIF-induced pulmonary inflammation. Respiratory Research, 10, [33]. https://doi.org/10.1186/1465-9921-10-33

CBE

Takahashi K, Koga K, Linge H, Zhang Y, Lin X, Metz CN, Al-Abed Y, Ojamaa K, Miller EJ. 2009. Macrophage CD74 contributes to MIF-induced pulmonary inflammation. Respiratory Research. 10:Article 33. https://doi.org/10.1186/1465-9921-10-33

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Vancouver

Author

Takahashi, Koichiro ; Koga, Kiyokazu ; Linge, Helena ; Zhang, Yinzhong ; Lin, Xinchun ; Metz, Christine N ; Al-Abed, Yousef ; Ojamaa, Kaie ; Miller, Edmund J. / Macrophage CD74 contributes to MIF-induced pulmonary inflammation. In: Respiratory Research. 2009 ; Vol. 10.

RIS

TY - JOUR

T1 - Macrophage CD74 contributes to MIF-induced pulmonary inflammation

AU - Takahashi, Koichiro

AU - Koga, Kiyokazu

AU - Linge, Helena

AU - Zhang, Yinzhong

AU - Lin, Xinchun

AU - Metz, Christine N

AU - Al-Abed, Yousef

AU - Ojamaa, Kaie

AU - Miller, Edmund J

PY - 2009/5/4

Y1 - 2009/5/4

N2 - BACKGROUND: MIF is a critical mediator of the host defense, and is involved in both acute and chronic responses in the lung. Neutralization of MIF reduces neutrophil accumulation into the lung in animal models. We hypothesized that MIF, in the alveolar space, promotes neutrophil accumulation via activation of the CD74 receptor on macrophages.METHODS: To determine whether macrophage CD74 surface expression contributes MIF-induced neutrophil accumulation, we instilled recombinant MIF (r-MIF) into the trachea of mice in the presence or absence of anti-CD74 antibody or the MIF specific inhibitor, ISO-1. Using macrophage culture, we examined the downstream pathways of MIF-induced activation that lead to neutrophil accumulation.RESULTS: Intratracheal instillation of r-MIF increased the number of neutrophils as well as the concentration of macrophage inflammatory protein 2 (MIP-2) and keratinocyte-derived chemokine (KC) in BAL fluids. CD74 was found to be expressed on the surface of alveolar macrophages, and MIF-induced MIP-2 accumulation was dependent on p44/p42 MAPK in macrophages. Anti-CD74 antibody inhibited MIF-induced p44/p42 MAPK phosphorylation and MIP-2 release by macrophages. Furthermore, we show that anti-CD74 antibody inhibits MIF-induced alveolar accumulation of MIP-2 (control IgG vs. CD74 Ab; 477.1 +/- 136.7 vs. 242.2 +/- 102.2 pg/ml, p < 0.05), KC (1796.2 +/- 436.1 vs. 1138.2 +/- 310.2 pg/ml, p < 0.05) and neutrophils (total number of neutrophils, 3.33 +/- 0.93 x 104 vs. 1.90 +/- 0.61 x 104, p < 0.05) in our mouse model.CONCLUSION: MIF-induced neutrophil accumulation in the alveolar space results from interaction with CD74 expressed on the surface of alveolar macrophage cells. This interaction induces p44/p42 MAPK activation and chemokine release. The data suggest that MIF and its receptor, CD74, may be useful targets to reduce neutrophilic lung inflammation, and acute lung injury.

AB - BACKGROUND: MIF is a critical mediator of the host defense, and is involved in both acute and chronic responses in the lung. Neutralization of MIF reduces neutrophil accumulation into the lung in animal models. We hypothesized that MIF, in the alveolar space, promotes neutrophil accumulation via activation of the CD74 receptor on macrophages.METHODS: To determine whether macrophage CD74 surface expression contributes MIF-induced neutrophil accumulation, we instilled recombinant MIF (r-MIF) into the trachea of mice in the presence or absence of anti-CD74 antibody or the MIF specific inhibitor, ISO-1. Using macrophage culture, we examined the downstream pathways of MIF-induced activation that lead to neutrophil accumulation.RESULTS: Intratracheal instillation of r-MIF increased the number of neutrophils as well as the concentration of macrophage inflammatory protein 2 (MIP-2) and keratinocyte-derived chemokine (KC) in BAL fluids. CD74 was found to be expressed on the surface of alveolar macrophages, and MIF-induced MIP-2 accumulation was dependent on p44/p42 MAPK in macrophages. Anti-CD74 antibody inhibited MIF-induced p44/p42 MAPK phosphorylation and MIP-2 release by macrophages. Furthermore, we show that anti-CD74 antibody inhibits MIF-induced alveolar accumulation of MIP-2 (control IgG vs. CD74 Ab; 477.1 +/- 136.7 vs. 242.2 +/- 102.2 pg/ml, p < 0.05), KC (1796.2 +/- 436.1 vs. 1138.2 +/- 310.2 pg/ml, p < 0.05) and neutrophils (total number of neutrophils, 3.33 +/- 0.93 x 104 vs. 1.90 +/- 0.61 x 104, p < 0.05) in our mouse model.CONCLUSION: MIF-induced neutrophil accumulation in the alveolar space results from interaction with CD74 expressed on the surface of alveolar macrophage cells. This interaction induces p44/p42 MAPK activation and chemokine release. The data suggest that MIF and its receptor, CD74, may be useful targets to reduce neutrophilic lung inflammation, and acute lung injury.

KW - Animals

KW - Antigens, Differentiation, B-Lymphocyte

KW - Disease Models, Animal

KW - Histocompatibility Antigens Class II

KW - Humans

KW - Intramolecular Oxidoreductases

KW - Macrophage Migration-Inhibitory Factors

KW - Macrophages

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Pneumonia

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1186/1465-9921-10-33

DO - 10.1186/1465-9921-10-33

M3 - Article

C2 - 19413900

VL - 10

JO - Respiratory Research

JF - Respiratory Research

SN - 1465-9921

M1 - 33

ER -