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.
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.
Authors: Laurent Benayoun; Anne Druilhe; Marie-Christine Dombret; Michel Aubier; Marina Pretolani Journal: Am J Respir Crit Care Med Date: 2003-01-16 Impact factor: 21.405
Authors: Christopher E Brightling; Peter Bradding; Fiona A Symon; Stephen T Holgate; Andrew J Wardlaw; Ian D Pavord Journal: N Engl J Med Date: 2002-05-30 Impact factor: 91.245
Authors: P R Johnson; M Roth; M Tamm; M Hughes; Q Ge; G King; J K Burgess; J L Black Journal: Am J Respir Crit Care Med Date: 2001-08-01 Impact factor: 21.405
Authors: Patrick Berger; Pierre-Olivier Girodet; Hugues Begueret; Olga Ousova; Diahn-Warng Perng; Roger Marthan; Andrew F Walls; J Manuel Tunon de Lara Journal: FASEB J Date: 2003-09-18 Impact factor: 5.191
Authors: R Saunders; A Sutcliffe; D Kaur; S Siddiqui; F Hollins; A Wardlaw; P Bradding; C Brightling Journal: Clin Exp Allergy Date: 2009-09-07 Impact factor: 5.018