Fraktalkine produced by airway smooth muscle cells contributes to mast cell recruitment in asthma.
Human airway smooth muscle cells (HASMC) secrete fractalkine (FKN), a chemokine the concentration of which is increased in asthmatic patients. HASMC also induce mast cell chemotaxis, as a component of asthma inflammation. We therefore evaluated the role of smooth muscle-derived FKN in mast cell migration. We assessed the capacity of recombinant FKN to induce human mast cell chemotaxis. This effect implicates a calcium-independent pathway involving actin reorganization and protein kinase C-delta. We found that HASMC constitutively produce FKN, the synthesis of which is reinforced upon proinflammatory stimulation. Under basal experimental conditions, FKN production by HASMC is not sufficient to induce mast cell chemotaxis. However, pretreatment of mast cells with the neuropeptide vasoactive intestinal peptide (VIP) increases FKN potency to attract mast cells. Since we observed, in asthmatic patients, an increase in both FKN and VIP expression by airway smooth muscle and a positive correlation between VIP staining and mast cell infiltration of the smooth muscle layer, we conclude that HASMC-derived FKN may contribute to mast cell recruitment in asthma.
El-Shazly
Amr
A
Université Victor Segalen Bordeaux 2, Laboratoire de Physiologie Cellulaire Respiratoire, Institut National de la Santé et de la Recherche Médicale, E356, Bordeaux, France.
Berger
Patrick
P
Girodet
Pierre-Olivier
PO
Ousova
Olga
O
Fayon
Michael
M
Vernejoux
Jean-Marc
JM
Marthan
Roger
R
Tunon-de-Lara
J Manuel
JM
D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001980:Bronchi / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000096:biosynthesis / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D006801:Humans; D008407:Mast Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000276:immunology / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000096:biosynthesis / Q000235:genetics
C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D008565:Membrane Proteins; D014660:Vasoactive Intestinal Peptide; D011493:Protein Kinase C