Expression and function of endothelial monocyte-activating polypeptide-II in acute lung inflammation

Abstract.

Objective and design:

We tested the hypothesis that total endothelial monocyte-activating polypeptide-II (EMAP-II) expression (proEMAP/p43 and mature EMAP-II) is up-regulated in lipopolysaccharide (LPS)-induced acute lung inflammation (ALI) and that mature EMAP-II induces monocyte/macrophage and granulocyte recruitment in vivo.

Materials:

Thirty-five 10 week old, male Sprague-Dawley rats.

Treatment:

Animals were instilled intratracheally with 250 µg of E. coli LPS (N = 15) or saline (N = 5) or 20 µg of mature EMAP-II (N = 5).

Methods:

Total EMAP-II was quantified using ELISA and the protein was localized with light and electron microscopic immunocytochemistry in lungs of rats at 1, 3 and 12 h (n = 5/group).

Results:

ELISA showed increased total EMAP-II concentrations (p < 0.05) in lungs from LPS-treated rats compared to control animals. Compared to the controls, light and electron microscopic imunocytochemistry localized total EMAP-II in monocytes/macrophages and alveolar septa at 1 and 3 h and in vascular smooth muscles at 12 h post-LPS treatment. Instillation of mature EMAP-II increased lung monocytes/macrophages and granulocytes compared with control animals (p < 0.05). However, compared to the LPS treatment, mature EMAP-II instillation did not induce expression of IL-1β and MIP-2 (p < 0.05) and provoked less vigorous recruitment of monocytes/macrophages.

Conclusion:

EMAP-II expression is increased in LPS-induced ALI, and that intra-tracheal instillation of mature EMAP-II induces recruitment of monocytes/macrophages and granulocytes into the lungs without stimulating IL-1β or MIP-2 expression.