The alkaline sphingomyelinase (SMase) was first found in rat intestinal brush border. The important roles of this enzyme in digestion of sphingomyelin and in mucosal cell proliferation have been suggested. In the present work, the distribution of the alkaline SMase in the tissues of human beings and animals have been studied. By assaying the enzyme activity in human biopsy samples, we found that the alkaline SMase activity was absent in the stomach, increased in the duodenum, present at high levels in the small intestine, and slightly declined in the colon and rectum. High activities were found similarly in the intestinal contents of the healthy adults and infants. The activities were also found in the intestinal mucosa of rats, normal and germ-free mice, and hamsters with the same distribution pattern as in humans, but not in the intestinal mucosa of guinea pigs. Apart from the intestinal tract, a SMase activity preferring alkaline pH was identified in human and guinea pig bile, but not in the bile of rat, pig, sheep, and cow. No activity was found in either pancreatic tissue or pancreatic juice in all species tested, and none was detected in human urine and milk. In conclusion, alkaline SMase exists predominantly in the digestive system with considerable tissue and species differences.

No abstract

The activity of pancreatic enzymes declines during aboral intestinal transit. We tested the hypothesis that survival of pancreatic enzyme activities during intestinal transit is affected by amounts or concentrations of calories, nutrients, bile acids, or pancreatic enzymes entering the segments of the small intestine. An oroileal tube was placed in 26 healthy humans. The tube had duodenal, jejunal, and ileal infusion ports for nonabsorbable markers and aspiration ports in the distal duodenum, distal jejunum, and distal ileum. Four infusates of different proportions of protein, fat, and carbohydrate were infused continuously into the duodenum at 40, 90, and 160 kcal/h. Of the nutrients infused into the proximal duodenum, 21 +/- 3, 51 +/- 7, and 39 +/- 5% of fat, protein, and carbohydrate, respectively, were delivered to the distal duodenum. During duodenoileal transit, lipase, chymotrypsin, amylase, and trypsin lost 71 +/- 5, 63 +/- 5, 43 +/- 7, and 38 +/- 9% of activity, respectively (P < 0.01 vs. distal duodenum). During duodenojejunal transit, the activity of each enzyme decreased more than 35% (P < 0.01 vs. distal duodenum), and infusion of more calories into the duodenum improved survival of all enzymes except trypsin (P < 0.05). During jejunoileal transit, greater amounts and concentrations of calories and carbohydrate improved survival of only lipolytic activity (P < 0.01, P < 0.05, respectively), and loss of lipolytic activity correlated directly with delivery of bile acids (r = 0.56, P = 0.05) and chymotrypsin (r = 0.80, P = 0.001) to the distal jejunum. We conclude that intraluminal nutrients increase survival of enzyme activities in the proximal intestine. After absorption of nutrients, the action of chymotrypsin and bile acids decrease lipolytic activity more than activity of other enzymes.

Phospholipase A2 (PLA2) activity was measured in the serum of 23 individuals infused intravenously with endotoxin (EN) at a dose of 4 ng/kg body weight. A marked increase in PLA2 was noted 3 h after EN challenge (mean 828 +/- 513 units/ml), reached its maximum at 24 h after the challenge (mean 2667 +/- 2442 units/ml), and was still evident at 48 h (mean 763 +/- 366 units/ml). In contrast, TNF levels were maximal (mean 712 +/- 375 pg/ml) 90 min after the EN challenge and subsided to very low values (5 +/- 5 pg/ml) 5 h after the challenge. There was a positive correlation between the maximum response of TNF and that of PLA2 (r = 0.82, P < 0.01). Administration of ibuprofen or pentoxifylline did not alter the PLA2 response. EN challenge did not affect serum pancreatic PLA2 concentration or that of the lysosomal cationic enzyme, lysozyme. Neutralizing antibody against human recombinant (synovial type) PLA2 completely abolished PLA2 activity in the sera tested. We conclude that EN infusions cause marked intravascular release of nonpancreatic secretory PLA2 and that the magnitude of this response seems to be related to the prior generation of TNF.