Plasma Immunoreactive-Trypsin(ogen) Levels During Development

Levine, Jay F.; Jn, Udall; Kj, Bloch; Dg, Hanson; Bc, James; Walker, W. Allan

doi:10.1097/00005176-198805000-00016

Cited by 8 publications

(11 citation statements)

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“…These results confirm our previous findings (using an indirect method to assess plasma levels of a2-MG complexes) that healthy 3-d-old infants have elevated levels of complexes compared with adults (26). We suggest that increased plasma concentration in newborns may be a response to excessive protease uptake across an immature intestinal bamer (28) or may reflect delayed clearance of these complexes by the reticuloendothelial system. Future studies will be needed to assess a2-MGcomplex clearance in children and to determine whether the increased plasma levels of complexes lead to increased plasma proteolytic activity.…”

Section: Discussionsupporting

confidence: 90%

Intraarticular α2-Macroglobulin Complexes and Proteolytic Activity in Children with Juvenile Rheumatoid Arthritis

et al. 1993

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Section: Discussionsupporting

confidence: 90%

Intraarticular α2-Macroglobulin Complexes and Proteolytic Activity in Children with Juvenile Rheumatoid Arthritis

et al. 1993

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“…We have also demonstrated that this increased uptake of trypsin across the intestine may also occur in human newborns [4]. It has been suggested that, under certain circumstances, increased uptake may be responsible for protease-in duced liver disease [5].…”

Section: Introductionsupporting

confidence: 54%

Liver Uptake of Trypsin-Inhibitor Complexes; Differences between Suckling and Adult Rats

Levine

Pettei²

1991

Neonatology

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Previous studies have demonstrated increased intestinal trypsin uptake in newborn rats compared to adults. The mechanisms that protect tissues against proteolytic damage by trypsin include trypsin-inhibitor binding and subsequent liver uptake. In order to examine these mechanisms, bovine trypsin (1.25 mg/100 g body weight) plus trace ¹²⁵I-trypsin were injected into the portal vein of 2-week-old and adult rats. Liver, kidney and plasma ¹²⁵I activity were assessed at 1, 5 or 15 min following infusion and the different trypsin inhibitor fractions were separated and examined for ¹²⁵I activity. Newborn rats had significantly increased plasma levels of ¹²⁵I-trypsin and significantly decreased liver ¹²⁵I levels 1 min after infusion compared to adults. In addition, the slow decline in liver ¹²⁵I activity seen in the adult rats did not occur in the newborns. The pattern of trypsin-inhibitor binding was not significantly different at 1 5 and 15 min and there were no differences at these time intervals between newborns and adults. We suggest that the newborn liver is less effective in clearing infused trypsin leading to increased plasma levels, and this increased plasma trypsin concentration subsequently leads to increased liver levels of ¹²⁵I-trypsin. The increased trypsin levels in the liver may predispose newborns to protease-induced liver damage.

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“…Increased trypsin uptake in suckling rats is consistent with other studies demonstrat ing increased macromolecular uptake in newborn animals [1,2], We have suggested that increased trypsin uptake also occurs in human infants [3] and that the formation and clearance of trypsin-inhibitor complexes may be important in preventing trypsininduced organ damage [10]. Children with ai-PI deficiency may be especially suscepti ble to enzymes present in the intestine [4].…”

Section: Discussionsupporting

confidence: 87%

“…This finding is surprising in view of the increased a-MG complexes that we detected in human infants [10], presumably due at least in part to increased trypsin uptake [3], This finding can be explained by the differ ences in plasma inhibitors between humans and rats. Previously, we demonstrated [10] that the incubation of bovine trypsin with plasma generated a-MG complexes.…”

Section: Discussioncontrasting

confidence: 66%

“…An increased uptake of proteases across the intestine may also occur in human newborns. We have demonstrated that 3-day-old infants have el evated levels of immunoreactive trypsin(ogen) compared to adults and that some of this increased trypsin(ogen) may represent trypsin taken up from the intestinal lumen [3], We have also suggested that, in new borns, increased protease uptake may under certain circumstances be responsible for pro tease-induced liver disease and that breast milk, which contains protease inhibitors, may protect against proteolytic damage [4], Rat plasma contains several trypsin in hibitors with complex interactions with pro teases [5,6], The three most important in hibitors are ai-protease inhibitor (al-PI; 60 kD), di-inhibitor 3 (a r l3; 200 kD), and amacroglobulin (a-MG; 720 kD). Rat a-MG is a composite of two related macroglobu lins, ai and cu-MG.…”

Section: Introductionmentioning

confidence: 83%

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Trypsin Uptake and Trypsin-Inhibitor Complexes

Levine

Udall²,

Pettei³

et al. 1989

Neonatology

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Previous studies have suggested that both newborn animals and humans absorb intact proteases from the intestine in greater amounts than do adults. Absorbed proteases are rapidly complexed in plasma by several inhibitors which inactivate free proteases. In order to confirm increased intestinal uptake in newborns, we evaluated the plasma trypsin activity in both 2-week-old and adult rats following a trypsin feed. In addition, we studied the interaction between absorbed trypsin and rat trypsin inhibitors (α-macroglobulin, α₁-inhibitor 3, and α₁-protease inhibitor) by determining the concentration of α-macroglobulin complexes both in vivo and in vitro following trypsin feeding and by evaluating the amount of trypsin activity complexed with the different inhibitors. In vivo experiments demonstrated that trypsin uptake was significantly increased in newborns compared to adult rats and that 50–70% of plasma trypsin activity was associated with αi-inhibitor 3. Increased uptake was not accompanied by increased α-macroglobulin complexes. In vitro trypsin incubation did not lead to increased α-macroglobulin complexes until the other inhibitors were removed. These findings suggest that newborns have increased trypsin uptake, and the trypsin initially binds to α₁-inhibitor 3 before being transferred to α-macroglobulin for clearance. Further studies are needed in order to understand the interaction between intestinal uptake and plasma inhibition of absorbed proteases.

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Plasma Immunoreactive-Trypsin(ogen) Levels During Development

Cited by 8 publications

References 0 publications

Intraarticular α2-Macroglobulin Complexes and Proteolytic Activity in Children with Juvenile Rheumatoid Arthritis

Intraarticular α2-Macroglobulin Complexes and Proteolytic Activity in Children with Juvenile Rheumatoid Arthritis

Liver Uptake of Trypsin-Inhibitor Complexes; Differences between Suckling and Adult Rats

Trypsin Uptake and Trypsin-Inhibitor Complexes

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