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

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.

Group education sessions and compliance with nasal CPAP therapy.

STUDY OBJECTIVES: To determine an effective means of improving compliance with nasal continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA). DESIGN: Retrospective chart review. SETTING: An outpatient clinic at a Veterans Affairs Medical Center. PATIENTS: Seventy-three patients with OSA. INTERVENTIONS: Hour meters on CPAP machines provided documentation of nightly machine use. A 2-h group CPAP clinic, scheduled every 6 months, provided education, support, symptom treatment, and equipment monitoring for all CPAP patients. RESULTS: Twenty-five patients had hour meter readings taken at their first CPAP clinic. In these patients, nightly CPAP use increased from 5.2 +/- 0.6 to 6.3 +/- 0.6 h per night after attendance at one CPAP clinic (p < 0.05). CPAP use increased from 5.2 +/- 0.5 before CPAP clinic to 6.3 +/- 0.6 h per night after attendance at all subsequent CPAP clinics for 34 patients (p < 0.05), an improvement that was sustained over 605 +/- 34 days. Twenty-nine percent of patients increased nightly CPAP use by at least 2 h, while only 6% decreased by > or = 2 h (p < 0.025). Patients receiving supplemental oxygen had higher CPAP use prior to CPAP clinic compared to patients not receiving oxygen (p < 0.05). CONCLUSIONS: Attendance in a group clinic designed to encourage patient compliance with CPAP therapy provided a simple and effective means of improving treatment of OSA.

Mechanism of ATP-induced leukocyte adherence to cultured pulmonary artery endothelial cells.

Previously we have shown that ATP enhances the adherence of HL-60 cells and human neutrophils to bovine pulmonary artery endothelial cells. The current investigations extend earlier findings by showing that ATP and UTP dose-dependently stimulate human neutrophil adherence to human pulmonary artery endothelial cells. We have also explore the mechanisms of ATP- and UTP-stimulated adherence. We have found that fucose, a component of selectin receptors, inhibits ATP-stimulated HL-60 cell-bovine pulmonary artery endothelial cell adhesion. Additionally, pretreatment of HL-60 cells with neuraminidase abolishes ATP enhancement. However, fucose does not affect ATP- or thrombin-induced adhesion of freshly isolated human neutrophils to human endothelial cells. Antibodies to human P-selection intercellular adhesion molecule (ICAM)-1, and the beta-subunit of CD11/CD18 do not alter ATP-induced adherence of HL-60 cells to bovine endothelial cells. Similarly, antibodies to human P-selectin and ICAM-1 do not inhibit human neutrophil-human pulmonary artery endothelial cell adhesion. The platelet-activating factor receptor antagonists, WEB-2086 and L-659,989, are effective in attenuating ATP- and UTP-stimulated adherence. Preincubation of neutrophils or human pulmonary artery endothelial cells with ATP or UTP also enhances adherence, an effect that is blocked by L-659,989. Thus platelet activating factor, associated with both neutrophils and endothelial cells, mediates ATP- and UTP-induced neutrophil adherence. ATP, released during vascular injury, may exacerbate neutrophil-endothelial cell interaction and thereby contribute to neutrophil-induced injury.