• Life sciences · May 2012

    Role of CD69 in acute lung injury.

    • Shunsuke Ishizaki, Yoshitoshi Kasuya, Fuminobu Kuroda, Kensuke Tanaka, Junichi Tsuyusaki, Keita Yamauchi, Hirofumi Matsunaga, Chiaki Iwamura, Toshinori Nakayama, and Koichiro Tatsumi.
    • Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan. ishizaki@bj8.so-net.ne.jp
    • Life Sci. 2012 May 15; 90 (17-18): 657-65.

    AimsCD69 is an early activation marker in lymphocytes and an important signal transmitter in inflammatory processes. However, its role in acute lung injury (ALI) is still unknown. We used a lipopolysaccharide (LPS)-induced mouse model of ALI to study the role of macrophage-surface CD69 in this condition.Main MethodsWe investigated bronchoalveolar lavage fluid (BALF) cell subpopulations, myeloperoxidase levels in lung homogenates, lung pathology, and lung oedema in CD69-deficient (CD69(-/-)) mice 24h after LPS instillation. We also determined cytokine/chemokine expression levels in BALF and macrophage culture supernatant from CD69(-/-) and wild type (WT) mice. Also, we investigated CD69, keratinocyte-derived chemokine (KC) and macrophage inflammatory protein (MIP)-2 localization in the lungs after LPS administration. Furthermore, we examined the effect of anti-CD69 antibody on LPS-induced cytokine/chemokine release from cultured macrophages.Key FindingsOur study shows that intratracheal instillation of LPS-induced neutrophilic infiltration, histopathological changes, myeloperoxidase positivity, and oedema in the lung to a lower degree in CD69(-/-) mice than in WT mice. The immunoreactivities for CD69, KC and MIP2 were induced in the lung of WT mice instilled with LPS and were predominantly localized to the macrophages. Moreover, the cytokine/chemokine expression profile between the two genotypes of cultured macrophages in response to LPS was similar to that observed in the BALF. In addition, anti-CD69 antibody inhibited the LPS-induced cytokine/chemokine expression.SignificanceThese results suggest that CD69 on macrophages plays a crucial role in the progression of LPS-induced ALI and may be a potentially useful target in the therapy for ALI.Copyright © 2012 Elsevier Inc. All rights reserved.

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