ATP induced MUC5AC release from human airways in vitro.
BACKGROUND
Chronic airway diseases are often associated with marked mucus production, however, little is known about the regulation of secretory activity by locally released endogenous mediators.


OBJECTIVE
This investigation was performed to determine the release of MUC5AC mucin from human bronchial preparations using the purinergic agonists adenosine 5'-triphosphate (ATP) and uridine 5'-triphosphate (UTP).


METHODS
Immunohistochemical and immunoradiometric assays (IRMA) were used to detect the MUC5AC mucin. Immunohistochemical analysis were performed using individual 1-13 M1 and 21 M1 MAbs recognizing a recombinant M1 mucin partially encoded by the MUC5AC gene. IRMA measurments were performed using a mixture of eight anti-M1 mucin MAbs (PM8), which included both 1-13 M1 and 21 M1 MAbs. Lysozyme and protein were also measured in the biological fluids derived from human bronchial preparations obtained from patients who had undergone surgery for lung carcinoma.


RESULTS
The anti-M1 monoclonal antibodies labelled epithelial goblet cells. After challenge of human bronchial preparations with ATP, the goblet cells exhibited less staining. In contrast, UTP did not alter the immunolabelling of goblet cells. MUC5AC mucin in the bronchial fluids derived from ATP-challenged preparations was increased while UTP had no effect on release. ATP did not alter either the quantities of lysozyme or protein detected in the biological fluids.


CONCLUSIONS
These results suggest that ATP may regulate epithelial goblet cell secretion of MUC5AC mucin from human airways in vitro.
Roger
P
P
Laboratoire de Pharmacologie Pulmonaire CNRS ESA 8078, Le Plessis Robinson, France.
Gascard
J P
JP
Bara
J
J
de Montpreville
V T
VT
Yeadon
M
M
Brink
C
C
D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D046508:Culture Techniques; D006801:Humans; D007124:Immunoenzyme Techniques; D055271:Mucin 5AC; D009077:Mucins / Q000378:metabolism*; D009113:Muramidase / Q000378:metabolism; D014176:Protein Biosynthesis; D058913:Purinergic Agonists; D014544:Uridine Triphosphate / Q000378:metabolism / Q000494:pharmacology
C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D058913:Purinergic Agonists; D000255:Adenosine Triphosphate; D009113:Muramidase; D014544:Uridine Triphosphate