Nucleotide-induced PMN adhesion to cultured epithelial cells: possible role of MUC1 mucin

Accumulation of intraluminal polymorphonuclear leukocytes (PMN) is a hallma rk, of inflammatory diseases of the airways. Extracellular nucleotides stim ulate PMN adhesion to human main pulmonary artery endothelial cells (HPAEC) by a purinoceptor-mediated mechanism. We investigated the effects of nucle otides on adhesion of freshly isolated human PMN to cultured human tracheob ronchial epithelial cells (HBEC). We found that extracellular ATP and UTP w ere much less effective in stimulating PMN adhesion to HBEC compared with H PAEC, whereas the bacterial chemotactic peptide N-formyl-Met-Leu-Phe stimul ated PMN adhesion to both cell types to an equal degree. We investigated se veral mechanisms that might account for decreased nucleotide-induced PMN ad hesion to HBEC. The ectonucleotidase-resistant ATP analog adenosine 5'-O-(3 -thiotriphosphate) was also ineffective in stimulating PMN adhesion to HBEC , indicating that degradation of ATP by ectonucleotidase(s) was not respons ible for altered PMN adhesion. HBEC responded to ATP and UTP with increased intracellular calcium, indicating that these cells are capable of purinoce ptor-mediated responses. We found that ATP and UTP also did not stimulate P MN adhesion to Chinese hamster ovary (CHO) cells, which had been stably tra nsfected with the gene for hamster Mud, a cell-associated mucin. However, A TP and UTP did stimulate adhesion of PMN to nontransfected CHO cells. These results suggested that MUC1 mucin modulates PMN adhesion to epithelium. We found that cultured HBEC expressed more mRNA and protein for MUC1 mucin th an did HPAEC. We conclude that extracellular nucleotides are less effective in stimulating PMN adhesion to epithelial cells than to endothelial cells and that overexpression of hamster Mud mucin inhibits nucleotide-induced PM N adhesion to CHO cells.