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This Article Full Text Full Text (PDF) All Versions of this Article: 294/2/L214    most recent 00086.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Haley, K. J. Articles by Lilly, C. M. Search for Related Content PubMed PubMed Citation Articles by Haley, K. J. Articles by Lilly, C. M.

Ontogeny of the eotaxins in human lung

¹Department of Medicine, Brigham and Women's Hospital, and ²Department of Pathology, Brigham and Women's and Children's Hospitals, Boston, Massachusetts; ³Department of Medicine, National Maternity Hospital, Dublin, Ireland; ⁴Departments of Pathology and Medicine, Duke University, Durham, North Carolina; ⁵Division of Pulmonary and Critical Care Medicine, University of Maryland School of Medicine, Baltimore, Maryland

Submitted 7 March 2007 ; accepted in final form 20 November 2007

The ontogeny of the C-C chemokines eotaxin-1, eotaxin-2, and eotaxin-3 has not been fully elucidated in human lung. We explored a possible role for eotaxin in developing lung by determining the ontogeny of eotaxin-1 (CCL11), eotaxin-2 (CCL24), eotaxin-3 (CCL26), and the eotaxin receptor, CCR3. We tested discarded surgical samples of developing human lung tissue using quantitative RT-PCR (QRT-PCR) and immunostaining for expression of CCL11, CCL24, CCL26, and CCR3. We assessed possible functionality of the eotaxin-CCR3 system by treating lung explant cultures with exogenous CCL11 and analyzing the cultures for evidence of changes in proliferation and activation of ERK1/2, a signaling pathway associated with CCR3. QRT-PCR analyses of 22 developing lung tissue samples with gestational ages 10–23 wk demonstrated that eotaxin-1 mRNA is most abundant in developing lung, whereas mRNAs for eotaxin-2 and eotaxin-3 are minimally detectable. CCL11 mRNA levels correlated with gestational age (P < 0.05), and immunoreactivity was localized predominantly to airway epithelial cells. QRT-PCR analysis detected CCR3 expression in 16 of 19 developing lung samples. Supporting functional capacity in the immature lung, CCL11 treatment of lung explant cultures resulted in significantly increased (P < 0.05) cell proliferation and activation of the ERK signaling pathway, which is downstream from CCR3, suggesting that proliferation was due to activation of CCR3 receptors by CCL11. We conclude that developing lung expresses the eotaxins and functional CCR3 receptor. CCL11 may promote airway epithelial proliferation in the developing lung.

pulmonary development; embryonic; epithelium