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Intestinal capillaries. I. Permeability to peroxidase and ferritin
Abstract:
Horseradish peroxidase (mol. diam. approximately 50 A) and ferritin (mol. diam. approximately 110 A) were used as probe molecules for the small and large pore system, respectively, in blood capillaries of the intestinal mucosa of the mouse. Peroxidase distribution was followed in time, after intravenous injection, by applying the Graham-Karnovsky histochemical procedure to aldehyde-fixed specimens. The tracer was found to leave the plasma rapidly and to reach the pericapillary spaces 1 min post injection. Between 1 min and 1 min 30 sec, gradients of peroxidase reaction product could be demonstrated regularly around the capillaries; their highs were located opposite the fenestrated parts of the endothelium. These gradients were replaced by even distribution past 1 min 30 sec. Ferritin, followed directly by electron microscopy, appeared in the pericapillary spaces 3-4 min after i.v. injection. Like peroxidase, it initially produced transient gradients with highs opposite the fenestrated parts of the endothelium. For both tracers, there was no evidence of movement through intercellular junctions, and transport by plasmalemmal vesicles appeared less efficient than outflow through fenestrae. It is concluded that, in the blood capillaries of the inintestinal mucosa, the diaphragms of the endothelial fenestrae contain the structural equivalents of the small pore system. The large pore system seems to be restricted to a fraction of the fenestral population which presumably consists of diaphragm-free or diaphragm-deficient units.
Insights
Horseradish peroxidase and ferritin reveal distinct pore systems in mouse intestinal capillaries. Fenestral diaphragms form the small pore system, while diaphragm-free fenestrae constitute the large pore system.
Area of Science:
- Endothelial transport mechanisms
- Capillary permeability
- Gastrointestinal physiology
Background:
- Blood capillaries in the intestinal mucosa possess complex pore systems.
- Understanding these pores is crucial for nutrient and drug transport.
- Previous models lacked detailed structural correlation.
Purpose of the Study:
- To characterize the small and large pore systems in mouse intestinal capillaries.
- To identify the structural components responsible for selective permeability.
- To elucidate the transport pathways across the capillary endothelium.
Main Methods:
- Intravenous injection of horseradish peroxidase (50 A) and ferritin (110 A) as tracer molecules.
- Graham-Karnovsky histochemical staining for peroxidase localization.
- Direct electron microscopy for ferritin tracking.
- Analysis of tracer distribution over time post-injection.
Main Results:
- Horseradish peroxidase rapidly entered pericapillary spaces, with concentration gradients highest opposite fenestrated endothelium.
- Ferritin appeared later, also showing transient gradients near fenestrae.
- No evidence of tracer movement through intercellular junctions.
- Transport via fenestrae was more efficient than via plasmalemmal vesicles.
Conclusions:
- Endothelial fenestral diaphragms represent the small pore system in intestinal capillaries.
- The large pore system is likely mediated by diaphragm-free or deficient fenestrae.
- Fenestrae are the primary route for both small and large molecule transport across these capillaries.