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  • Title: Nucleotide-induced PMN adhesion to cultured epithelial cells: possible role of MUC1 mucin.
    Author: Rounds S, Likar LL, Harrington EO, Kim KC, Smeglin A, Heins K, Parks N.
    Journal: Am J Physiol; 1999 Nov; 277(5):L874-80. PubMed ID: 10564170.
    Abstract:
    Accumulation of intraluminal polymorphonuclear leukocytes (PMN) is a hallmark of inflammatory diseases of the airways. Extracellular nucleotides stimulate PMN adhesion to human main pulmonary artery endothelial cells (HPAEC) by a purinoceptor-mediated mechanism. We investigated the effects of nucleotides on adhesion of freshly isolated human PMN to cultured human tracheobronchial epithelial cells (HBEC). We found that extracellular ATP and UTP were much less effective in stimulating PMN adhesion to HBEC compared with HPAEC, whereas the bacterial chemotactic peptide N-formyl-Met-Leu-Phe stimulated PMN adhesion to both cell types to an equal degree. We investigated several mechanisms that might account for decreased nucleotide-induced PMN adhesion 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 responsible for altered PMN adhesion. HBEC responded to ATP and UTP with increased intracellular calcium, indicating that these cells are capable of purinoceptor-mediated responses. We found that ATP and UTP also did not stimulate PMN adhesion to Chinese hamster ovary (CHO) cells, which had been stably transfected with the gene for hamster Muc1, a cell-associated mucin. However, ATP 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 than 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 Muc1 mucin inhibits nucleotide-induced PMN adhesion to CHO cells.
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