Ontogeny of the eotaxins in human lung.
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.
Brigham and Women's Hospital, Division of Pulmonary and Critical Care Medicine, 75 Francis Street, Boston, MA 02115, USA. khaley@rics.bwh.harvard.edu
Kathleen J
KJ
Haley
Mary E
ME
Sunday
Yolanda
Y
Porrata
Colleen
C
Kelley
Anne
A
Twomey
Aliakbar
A
Shahsafaei
Benjamin
B
Galper
Larry A
LA
Sonna
Craig M
CM
Lilly
D049109:Cell Proliferation / Q000187:drug effects; D054413:Chemokine CCL11 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D054423:Chemokine CCL24 / Q000235:genetics / Q000378:metabolism; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000235:genetics* / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005865:Gestational Age; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000166:cytology / Q000196:embryology* / Q000201:enzymology / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054397:Receptors, CCR3 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
C120429:CCL26 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D054423:Chemokine CCL24; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D012333:RNA, Messenger; D054397:Receptors, CCR3; D048049:Extracellular Signal-Regulated MAP Kinases