The airway smooth muscle CCR3/CCL11 axis is inhibited by mast cells.
BACKGROUND
Airway smooth muscle hyperplasia is a feature of asthma, and increases with disease severity. CCR3-mediated recruitment of airway smooth muscle progenitors towards the airway smooth muscle bundle has been proposed as one possible mechanism involved in airway smooth muscle hyperplasia. Mast cells are microlocalized to the airway smooth muscle bundle and whether mast cells influence CCR3-mediated migration is uncertain.


METHODS
We examined the expression of CCR3 by primary cultures of airway smooth muscle cells from asthmatics and nonasthmatics. CCR3 function was examined using intracellular calcium measurements, chemotaxis, wound healing, cell proliferation and survival assays. We investigated the recovery and function of both recombinant and airway smooth muscle-derived CCL11 (eotaxin) after co-culture with beta-tryptase and human lung mast cells.


RESULTS
Airway smooth muscle expressed CCR3. Airway smooth muscle CCR3 activation by CCL11 mediated intracellular calcium elevation, concentration-dependent migration and wound healing, but had no effect on proliferation or survival. Co-culture with beta-tryptase or mast cells degraded recombinant and airway smooth muscle-derived CCL11, and beta-tryptase inhibited CCL11-mediated airway smooth muscle migration.


CONCLUSIONS
CCL11 mediates airway smooth muscle migration. However co-culture with beta-tryptase or mast cells degraded recombinant and airway smooth muscle-derived CCL11 and inhibited CCL11-mediated airway smooth muscle migration. Therefore these findings cast doubt on the importance of the CCL11/CCR3 axis in the development of airway smooth muscle hyperplasia in asthma.
Saunders
R
R
Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
Sutcliffe
A
A
Woodman
L
L
Kaur
D
D
Siddiqui
S
S
Okayama
Y
Y
Wardlaw
A
A
Bradding
P
P
Brightling
C
C
D001249:Asthma / Q000378:metabolism / Q000473:pathology*; D054413:Chemokine CCL11 / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D006965:Hyperplasia; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology; D054397:Receptors, CCR3 / Q000378:metabolism*; D012720:Severity of Illness Index
C515456:CCL11 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D054397:Receptors, CCR3