Mast cell adhesion to bronchial smooth muscle in asthma specifically depends on CD51 and CD44 variant 6.
BACKGROUND
Mast cells infiltrate the bronchial smooth muscle (BSM) in asthmatic patients, but the mechanism of mast cell adhesion is still unknown. The adhesion molecules CD44 (i.e. hyaluronate receptor) and CD51 (i.e. vitronectin receptor) are widely expressed and bind to many extracellular matrix (ECM) proteins. The aims of the study are (i) to identify the role of ECM in mast cell adhesion to BSM and (ii) to examine the role of CD51 and CD44 in this adhesion.


METHODS
Human lung mast cells, human mast cell line (HMC-1), and BSM cells from control donors or asthmatic patients were cultured in the presence/absence of various cytokines. Mast cell-BSM interaction was assessed using (3)H-thymidine-pulsed mast cells, confocal immunofluorescence, or electron microscopy. Adhesion molecules expression and collagen production on both cell types were evaluated by quantitative RT-PCR, western blot, and flow cytometry.


RESULTS
Mast cell adhesion to BSM cells mostly involved type I collagen of the ECM. Such an adhesion was increased in normal BSM cells under inflammatory condition, whereas it was maximal in asthmatic BSM cells. Blockade of either CD51 or CD44 significantly decreased mast cell adhesion to BSM. At the molecular level, protein and the transcriptional expression of type I collagen, CD51 or CD44 remained unchanged in asthmatic BSM cells or in mast cells/BSM cells under inflammatory conditions, whereas that of CD44 variant isoform 6 (v6) was increased.


CONCLUSIONS
Mast cell-BSM cell adhesion involved collagen, CD44, and CD51, particularly under inflammatory conditions. CD44v6 expression is increased in asthmatic BSM cells.
Girodet
P-O
PO
Université de Bordeaux, Bordeaux, France. pierre-olivier.girodet@pharmaco.u-bordeaux2.fr
Ozier
A
A
Trian
T
T
Begueret
H
H
Ousova
O
O
Vernejoux
J-M
JM
Chanez
P
P
Marthan
R
R
Berger
P
P
Tunon de Lara
J M
JM
D000368:Aged; D001249:Asthma / Q000378:metabolism / Q000503:physiopathology*; D001980:Bronchi / Q000166:cytology* / Q000503:physiopathology; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D039564:Integrin alphaV / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000502:physiology*
D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D039564:Integrin alphaV