Intestinal morphology, marker enzymes and lipid content of brush border membranes from rabbit jejunum and ileum: effect of aging

Aging is associated with changes in the intestinal uptake of nutrients. This study was undertaken to determine whether the morphology, enzyme markers and the lipid content of the intestinal brush border membrane (BBM) was influenced by aging. There was an increase in the height of the jejunal villi and number of cells/villus, resulting in an age-related increase in the jejunal villus and mucosal surface area in young as compared with weanling rabbits. In mature 1-year-old animals, there was a decline in villus height, number of cells/villus, and mucosal surface area, so that the jejunal characteristics of the mature animals resembled those of the weanling rabbits. In the ileum, aging was associated with an increase (weanling vs. young), then a decrease (young vs. mature) in the height of the villi, and the number of cells/villus. Aging had no effect on the size of the villus cells. At all ages there was a direct positive relationship between the height of the villi and the mucosal surface area, and between villus surface area and sucrase activity. An established technique was used to purify rabbit BBM and to measure the BBM content of enzyme markers and lipids in weanling, young and mature animals. Both the BBM sucrase (S) and alkaline phosphatase (AP) increased in young as compared with weanling rabbits, and the ratio of AP/S remained unchanged. The S remained high in mature rabbits, but AP declined, so that AP/S fell. There was a positive linear correlation between S and villus surface area. In weanling rabbits, the total BBM phospholipid content and the ratio of total phospholipid/total cholesterol were lower in the ileum than in the jejunum. In the jejunal BBM of young animals, there was more total free fatty acids and cholesterol ester than in the weanling jejunum. The jejunal BBM total phospholipids and total cholesterol were higher in the mature than in the weanling animal jejunum when expressed as nmoles/mg protein, but the ratio of total phospholipid/total cholesterol was unaffected by aging. The greatest percentage of jejunal BBM phospholipid was comprised of lecithin and phosphatidyl ethanolamine. The increased BBM total phospholipid content in mature animals was associated with a higher amount and lower proportion of lecithin, but a higher proportion of sphingomyelin and phosphatidyl serine.(ABSTRACT TRUNCATED AT 400 WORDS)     

Measurements of intestinal villi non-specific and ulcer-associated duodenitis-correlation between area of microdissected villus and villus epithelial cell count.

Measurements of villus height, villus area, together with counts of epithelial cells in individual villi, were performed on endoscopic duodenal biopsies from five groups of patients: controls, ulcer-associated duodenitis, mild and severe non-specific (non-ulcerative) duodenitis, cimetidine healed ulcer-associated duodenitis and cimetidine healed non-specific duodenitis. The objectives of the study were two-fold: to establish if epithelial cell count correlated with simpler measurements of villus height or area; and to compare the findings in ulcer-associated and in non-specific duodenitis. Villus area correlated well with epithelial cell count per villus (r = 0.96); villus height correlated less well (r = 0.66). When compared with controls, there was a significant decrease in the epithelial cell count per villus in ulcer-associated and severe non-specific duodenitis, but this was confined to the visually inflamed area of the duodenal bulb. After healing of inflammation with cimetidine villus height, area, and epithelial cell count returned to values similar to those in controls. This study confirms that the effects of ulcer-associated and severe non-specific duodenitis on duodenal villi are identical.     

Site of thyroxine-evoked decrease of jejunal lactase in the rat

Localization of thyroid-mediated decrease of lactase activity along the villus-crypt unit in adult rat jejunum was studied 24 and 48 h after first injection of L-thyroxine (200 micrograms/100 g body wt) every 24 h. [3H]thymidine was also given at time of first thyroxine injection. Serum thyroid-stimulating hormone, food intake, and body weight were significantly decreased within 24 h. Total jejunal protein and villus-crypt height were unchanged during the time period studied. Lactase activity (expressed both as per tissue protein and per intestinal segment) was significantly decreased in jejunum and midjejunum within 24 h. Serial sectioning of the jejunal villus-crypt unit in a cryostat showed that the site of decrease in lactase activity at 24 h was in the apical villus and by 48 h extended along the entire height of the villus. Epithelial cell migration measured both by histoautoradiography and scintillation counting of [3H]thymidine in cryostat sections revealed no difference between control and thyroid-treated animals at both 24 and 48 h. The decrease in lactase activity at 24 h was in advance of the leading edge of radioactivity, indicating that the thyroid-evoked response occurred in mature enterocytes already on the villus.     

Factors influencing villus size in the small intestine of adult rats as revealed by transposition of intestinal segments

As an index of villus size, the number of epithelial cells per representative villus section was counted in longitudinal sections of the rat small intestine. Villus size was found to decrease gradually along the length of the small intestine, with villi being nearly three times as large in upper duodcnum as in terminal ileum. The influence of various surgical operations on villus size was then examined. In ileal segments inserted into the jejunum, villi enlarged to the size of local jejunal villi. In jejunal segments inserted into the ileum, villi decreased almost to the size of local ileal villi. Thus, villus size was influenced by the environment, that is, most probably by the different types of chyme in jejunum and ileum. In duodenal segments inserted into the ileum, villi did not decrease in size, and distally located ileal villi enlarged. This and other experiments indicated that the duodenum produced secretions which not only neutralized the villus-reducing effect of the ileal environment, but also exerted a potent villus-enlarging effect. Pyloric secretions had a similar villus-enlarging effect. Segments of intestine were made into blind sacs by closing their proximal end and joining their distal end to the colon, so as to remove the influence of the chyme. Villus size decreased in sacs of jejunum and lower duodenum (without the duodenal papilla), but increased in sacs of ileum. Thus in the three types of sacs, there was a tendency for villi to acquire an intermediate size. In conclusion, an intermediate villus size, which is postulated to exist in chyme-free, non-functional intestine, would normally be modified by two types of factors: villusenlarging factors present mainly in pyloric and duodenal secretions, and villus-reducting factors present in the ileal chyme. Interaction between these factors would result in the gradient of villus size along the small intestine.     

A region of mitochondrial division in the epithelium of the small intestine of the rat

Electron microscopic examination of samples from various regions of the rat small intestine was carried out. The number of mitochondria in the epithelial cells was estimated. The counts were made in sections of cells cut along their longitudinal central plane. The errors involved in extrapolating these counts to the whole cells were also estimated. The average mitochondrial number per cell section was 21 in the lower third of the crypts, it gradually increased in the mid and upper thirds and reached about double, 42, at the villus base. The known forms of dividing mitochondria were identified in the mid and upper third of the crypts. The counts remained around 42 along the epithelium of the villi. Crypt cells are continually produced in the lower crypt; these cells migrate to the villi while differentiating into nonproliferative absorptive cells. After inhibiting mitosis by methotrexate, this migration continued (Altmann, 1974) and mitochondrial division persisted. In segments of the jejunum isolated surgically from the functional intestine for three weeks, mitosis and cell migration continued, but no evidence of mitochondrial duplication was found. Each mitochondrion probably undergoes a division as the crypt cells migrate from the mid-crypts to the villus. As a result, the villus epithelial cells contain double numbers of mitochondria. It appears that the mitochondrial division is not directly related to mitosis and is elicited by a stimulus present only in the functional intestine.     

A region of mitochondrial division in the epithelium of the small intestine of the rat.

Electron microscopic examination of samples from various regions of the rat small intestine was carried out. The number of mitochondria in the epithelial cells was estimated. The counts were made in sections of cells cut along their longitudinal central plane. The errors involved in extrapolating these counts to the whole cells were also estimated. The average mitochondrial number per cell section was 21 in the lower third of the crypts, it gradually increased in the mid and upper thirds and reached about double, 42, at the villus base. The known forms of dividing mitochondria were identified in the mid and upper third of the crypts. The counts remained around 42 along the epithelium of the villi. Crypt cells are continually produced in the lower crypt; these cells migrate to the villi while differentiating into nonproliferative absorptive cells. After inhibiting mitosis by methotrexate, this migration continued (Altmann, '74) and mitochondrial division persisted. In segments of the jejunum isolated surgically from the functional intestine for three weeks, mitosis and cell migration continued, but no evidence of mitochondrial duplication was found. Each mitochondrion probably undergoes a division as the crypt cells migrate from the mid-crypts to the villus. As a result, the villus epithelial cells contain double numbers of mitochondria. It appears that the mitochondrial division is not directly related to mitosis and is elicited by a stimulus present only in the functional intestine.     

The stem-cell zone of the small intestinal epithelium. IV. Effects of resecting 30% of the small intestine

In the mouse jejunum, as in the rat, a new steady state was established 3 weeks after resection of 30% of the small intestine. The mean height of a villus, crypt, and proliferative zone increased. We studied the effects of this new steady state on the distribution of the four main epithelial cell types and on the stem-cell zone. Beginning 2 cm distal to the ligament of Treitz, 10 cm of jejunum were resected. In control animals the jejunum was transected 12 cm distal to the ligament of Treitz and then rejoined. The mice were killed 1 and 3 weeks after surgery and a piece of jejunum 4 cm distal to the anastomosis collected. One hour before death the animals were given an injection of 1 μCi/gm ³H-thymidine. The tissue was embedded in Epon and then serial 1 μm sections were prepared and radioautographed. One week after resection there was a transient increase in the proportion of enteroendocrine cells in the crypts. This returned to control levels 3 weeks after resection. Thus, there appeared to be a feedback from the enteroendocrine population onto enteroendocrine cell production. After resection, amplification of mucous cell numbers by mucous cell division was reduced and yet normal proportions of mucous cells were observed in the epithelium. Therefore, an increased proportion of stem-cell output must have been committed to the mucous and enteroendocrine cell lines. The increased height of the proliferative zone that followed 30% resection was not due to an increase in the number of transit divisions through the proliferative zone. Instead it was due to an increased output from the stem-cell zone into the proliferative zone. Evidence was presented which indicates that the increased output from the stem-cell zone was due to an increased number of stem cells in the zone, at the expense of non-stem cells. The height of the stem-cell zone, as indicated by the Paneth cell distribution, the mucous cell distribution, and the distribution of labeled mucous cells, did not change after 30% resection.     

Whole population cell kinetics and postnatal development of the mouse intestinal epithelium

Measurements of whole population cell kinetics of mouse intestinal epithelium during postnatal development are reported. Swiss albino mice aged 1, 2, 3, 4, 6, 8, 10, 12, 16, 19, 24, and 28 weeks were studied. Isolated epithelial preparations of jejunum and colon were used. Most kinetic parameters studied either increased or decreased with age to reach a steady level sometime after weaning. For example, before weaning about 30% of crypts were observed to be branching, while after weaning, the population of crypts that were branching decreased to adult levels of 5-10% in jejunum and 1-2% in colon. Thus, there was very active crypt formation before weaning, which likely continued into adult life but at a lower level. Villus formation appeared to be occurring in animals before weaning (i.e., 1-3 weeks), while it stopped with weaning, and thus the mean villus height increased to a plateau, which was constant with age after 4 weeks. In contrast, the mean villus width increased steadily with age. As the width of villi increased with age, the number of crypts associated with a villus also increased (presumably as a result of net crypt production in the adult). These measurements and many others (proportion of cells in S phase, number of cells/cm2, number of cells/villus, number of cells/crypt, etc.) are described.     

Whole population cell kinetics of mouse duodenal,jejunal, iieal,and colonic epithelia as determined by radioautography and flow cytometry

We report methods for the determination of whole population cell kinetics in the mouse intestinal epithelium by means of radioautography and flow cytometry. Epithelium was isolated from the four regions of the mouse intestine by the perfusion method described in Bjerknes and Cheng (1981a). Two experimental series were performed. In the first series, the tissue from one set of animals was fixed in 3.5% paraformaldehyde, dissociated by serial filtration, and then processed for flow cytometry. In the second series, fixed epithelium from a second set of animals was dissociated by gentle pipetting and then used to prepare dried cell suspensions on slides which were radioautographed. The whole population kinetic parameters determined by the two techniques, flow cytometry and radioautography, were not significantly different, indicating the reliability of both techniques for whole population kinetics determinations. In all regions of the intestinal tract, 12–14% of epithelial cells were in the S-phase. From this value, the whole epithelial turnover time was calculated to be about 60 hours in all regions of the intestine. The whole epithelial growth fraction was calculated to be 0.23 for the small intestinal epithelium and 0.31 for the colonic epithelium. Detailed analysis of the flow cytometric data showed that there were significantly more cells in early S-phase than in mid and late S-phase. From the isolated epithelial sheets a mean number of crypts per villus was determined for the duodenum, jejunum, and ileum. Single villi and crypts were microdissected for the preparation of squashes. From the squashes a mean number of cells per villus as well as per crypt was determined. From the results, the ratio of the number of epithelial cells in the villus population to the number of cells in the crypt population was determined to be 1.41, 1.31, 1.36 in duodenum, jejunum, and ileum, respectively. The proportion of the three main epithelial cell types, columnar, mucous, and Paneth, was determined with the dried cell suspension preparations. There was a decreasing gradient in the proportion of columnar cells from the proximal to the distal intestine while an increasing gradient was observed in the proportion of mucous cells. We found that mucous cell divisions account for only one half of mucous cell production in the small intestine. In the colonic epithelium, mucous cell divisions account for two-thirds of mucous cell production. This was in agreement with previous findings.     

Rat small intestinal mucins: a quantitative analysis

Although much is known about the qualitative distribution of mucin-secreting goblet cells in the small intestine, the quantitative distribution of stored mucins remains undefined. The purpose of this study was to determine the distribution of neutral stored mucin in the rat small intestine by using morphometric techniques and once established, to verify that this methodology could detect secretion in animals exposed to a known mucin secretagogue. Twelve male Wistar rats (five baseline, five pilocarpine-treated, and two vehicle controls) were fixed by vascular perfusion. After a brief fixation the intestine was removed, cut into 10 equal segments, sliced, and fixed overnight. Methacrylate sections from each segment were stained with periodic acid-Schiff and toluidine blue. For morphometry, the volume of epithelium per surface area of epithelial basal lamina was calculated with a Merz grid. The volume density of stored mucin per epithelium was determined by point-counting on a square lattice grid. Volumes were related to either surface area of epithelial basal lamina or mucosal surface area. Due mostly to contributions by villus stored mucin, the total amount of product was found to increase proximally to distally in the small bowel, with the most dramatic increases occurring in the first three segments. When subjected to pilocarpine, a massive secretory response was evoked, resulting in a near total depletion of crypt stored mucin at all levels of the small bowel. Secretion of villus stored mucin also occurred throughout the small intestine, however reaching levels of significance at only a few points. This study describes the distribution of stored mucin in the small intestine under baseline and accelerated secretory conditions.     

Effect of different single feeding diets on small intestinal mucosa of cocks: a histomorphometrical study

Diet composition as a major factor can affect histological status of the gut. The present study was conducted to evaluate histological changes of small intestinal wall of cockerels fed with high protein, high carbohydrate, or high fiber single diets. To this end, thirty Rhode Island Red cockerels, 70 weeks of age, were randomly allocated into three equal groups and hull-less barley, soybean meal, and sunflower meal supplemented to the basal diet of each group gradually during first week. Birds were fed with 100 % of each of the above diets for the next 2 weeks. At the end of the third week, all birds were sacrificed and small intestines were removed immediately and processed for histological study. Transverse sections from the middle parts of duodenum, jejunum, and ileum were made and stained with H&E and PAS for light microscopic study. Villus height, villus width, crypt depth, villus height/crypt depth ratio, and goblet cell number per unit area were determined. Data were analyzed by one-way ANOVA method. While hull-less barley and soy bean meal diets had no undesirable effect on histological parameters of small intestine, sunflower meal significantly decreased villus height/crypt dept ratio which may decrease nutrient absorption. In conclusion, single feeding with sunflower meal, but not hull-less barley and soy bean meal diets, adversely affects histological feature of intestinal mucosa of cockerels which may lead to decreased nutrient absorption and subsequently declined performance of the birds.     

Influence of starvation and refeeding on mucosal size and epithelial renewal in the rat small intestine

Adult male rats were fasted for 0 (controls), three, five and seven days; a group was refed for one day after six days of starvation. Histological samples were taken from five regions along the length of the small intestine. The sizes of the villi, crypts and mitotic pool were estimated by measuring the number of epithelial cells per villus and crypt section and the number of mitotic figures per crypt section. Additional studies were carried out using colchicine for estimating mitotic time and methotrexate for inhibiting mitosis. All three parameters decreased progressively during starvation; the decrease in villus size was most pronounced in the duodenum and gradually less distalward. Refeeding increased the mitotic pool in every region; crypt size did not increase and villus size increased slightly in duodenum and jejunum only. When refeeding was combined with mitotic inhibition, the cell population of the crypts became depleted by 30–40% without change in villus size; thus, renewal appeared to continue by crypt cells migrating to the villi. Mitosis in the crypts is used for epithelial renewal in the adult intestine. The calculated turnover time of the epithelium was longer than normal and similar in every stage of starvation. Refeeding appeared to stimulate renewal. Since villus size changed somewhat independently from mitotic activity, the involvement of a separate mechanism controlling villus size was indicated.     

Antigen-induced mucosal damage and restitution in the small intestine of the immunized rat

Intestinal mucosal damage and restitution were examined following antigen-induced systemic anaphylaxis in Nippostrongylus brasiliensis immunized rats. The rats were injected intravenously with N. brasiliensis antigen or saline. At 60 min, morphological and biochemical parameters were determined in jejunum and ileum, and the epithelial permeability was assessed by measuring recovery of 51Cr-ethylenediaminetetraacetic acid in the blood after injecting it into a ligated segment. Antigen challenge resulted in significant abnormalities: (1) villus damage with sloughing of enterocytes; (2) decreased activities of brush border enzymes; (3) decreased levels of mucosal histamine and rat mast cell protease II (mast cell mediators), and (4) increased uptake of 51Cr-ethylenediaminetetraacetic acid. Progression of the injury was examined by taking consecutive biopsies at 15-min intervals for 60 min and then at 5 h. At 15 min, an abnormality was present in all sections which ranged from minor oedema and enterocyte detachment at villus tips to virtual complete destruction of the apical region. Restitution occurred by villus contraction with migration of the epithelium over the damaged regions. At 5 h, the epithelium had resealed, but the villi were significantly reduced in height.     

Distribution of diazo-positive (argentaffin) cells in the small intestine of rats of various ages

In unit lengths of longitudinally cut histological sections of the rat small intestine, the number of diazo-positive argentaffin cells was determined along with the number of other epithelial cells. From these results, the frequency of argentaffin cells among the epithelial cells was calculated. The number, as well as the frequency, was maximal in the proximal duodenum and progressively decreased to a minimum in the mid-intestine. Thereafter, it increased progressively caudally to reach a second maximum in the terminal ileum. The frequency in the terminal ileum was almost as high as in the proximal duodenum. When calculated for the duodenum of various age groups, it decreased from eight to two argentaffin cells per 1000 epithelial cells from newborn to adult ages respectively. It was calculated furthermore that the total number of diazo-positive argentaffin cells in the rat small intestine should be around six million. Considering that the argentaffin cells are renewed about every four days (Ferreira and Leblond, ′71), about 1.5 million of them should be formed as well as exfoliated daily. The cells in the villi were stained more intensely than in the crypts, indicating that the argentaffin cells accumulate granules as they migrate from the crypts toward the villus tips, where indeed, intensely stained exfoliating argentaffin cells were occasionally observed. It is suggested that the exfoliation of argentaffin cells full of granules may be a mode of secretion for 5-hydroxytryptamine into the intestinal lumen.     

大鼠小肠嗜银、亲银细胞的分布及形态学观察

本文用肠卷石蜡切片的嗜银反应(黄荫乔法)、亲银反应(Singh法),对11只大鼠小肠的嗜银、亲银细胞的分布及形态学作了初步观察,结果如下。 1.大鼠小肠的嗜银、亲银细胞的密度,在十二指肠最高,从空肠到回肠逐渐减少。 2.嗜银、亲银细胞在肠腺基底部着色较浅,在腺上部着色加深,在绒毛顶端为深染。嗜银细胞基底部有突起,穿过基膜到达固有层。在固有层内,于突起附近有嗜银颗粒和突起相延续。嗜银颗粒到达细胞顶端较为多见,有时可见到嗜银颗粒释放到腺腔内。因此我们认为,嗜银、亲银细胞兼有内、外分泌双重功能。 3.在小肠固有层的结缔组织内,发现有嗜银细胞,细胞形状不规则,有突起,胞质和突起都充满嗜银颗粒,有时可见嗜银颗粒到达细胞外。颗粒的形态、致密度及染色特点,与上皮细胞之间的嗜银细胞相同,故这些细胞可能属于内分泌细胞。     

Light and scanning electron microscopic observations of the effects of sublethal doses of methotrexate on the rat small intestine

The small intestines of adult rats were examined by light and scanning-electron microscopy after sublethal doses of methotrexate were injected at 5, 3 and 1 mg, respectively, per rat per day, for three days. Methotrexate inhibited mitosis and thereby disrupted the steady state system of the epithelium. Villi and crypts progressively diminished up to about four and one-half days after the initial injection. Thereafter, recovery began and, by day 7, relatively normal morphology was restored. In the degenerative phase, the loss of crypt-villus continuum was frequently observed, the former crypts forming cyst-like structures. The columnar cells became flat and pleomorphic but epithelial continuity was maintained. Goblet cells apparently decreased in number. Paneth cells, especially in the ileum, appreciably increased in size and number. During the recovery phase, the cystic crypts apparently re-established continuity with the villus epithelium. Size and proportion of all epithelial cell types returned to normal. Scanning electron microscopy showed villus fusion and the cellular pleomorphism and loss of microvilli during the degenerative phase. During recovery of the villi some alteration in orientation and shape remained as shown by scanning electron microscopy.     

The future of Nomina Anatomica—a personal view

The small intestines of adult rats were examined by light and scanning-electron microscopy after sublethal doses of methotrexate were injected at 5, 3 and 1 mg, respectively, per rat per day, for three days. Methotrexate inhibited mitosis and thereby disrupted the steady state system of the epithelium. Villi and crypts progressively diminished up to about four and one-half days after the initial injection. Thereafter, recovery began and, by day 7, relatively normal morphology was restored. In the degenerative phase, the loss of crypt-villus continuum was frequently observed, the former crypts forming cyst-like structures. The columnar cells became flat and pleomorphic but epithelial continuity was maintained. Goblet cells apparently decreased in number. Paneth cells, especially in the ileum, appreciably increased in size and number. During the recovery phase, the cystic crypts apparently re-established continuity with the villus epithelium. Size and proportion of all epithelial cell types returned to normal. Scanning electron microscopy showed villus fusion and the cellular pleo-morphism and loss of microvilli during the degenerative phase. During recovery of the villi some alteration in orientation and shape remained as shown by scanning electron microscopy.     

Morphometric analysis of the effects of antineoplastic drugs on mucosa of normal ileum and ileal anastomoses in rats.

Antineoplastic agents affect the healing of intestinal anastomoses. They often induce anorexia and diarrhea, possibly caused by morphological changes in the small intestinal mucosa. These changes were evaluated in the rat ileum. Animals in group I underwent only intestinal surgery while those in groups II and III underwent surgery on the third day of a 5-day course with cisplatin (in two different doses), bleomycin, and 5-fluorouracil. The parameters were: number of mitoses in crypts, crypt depth, villus height, width, and contour length, measured in the mucosa of primarily resected segments of the ileum and of the anastomotic area. Surgery yields an increased crypt depth and villus length in the anastomotic area without changing villus width. The changes in intestinal crypts precede those in villi. Antineoplastic drugs decrease crypt mitotic rate, villus height, width, and contour length. After cessation of antineoplastic chemotherapy mitotic activity increases. The shallower and shorter villi increase in width and length resulting in an increased villus contour length and area. A linear relation exists between villus contour length and villus height and width. Thus, antineoplastic polychemotherapy, dose-dependently, reduces and surgical trauma increases intestinal proliferative activity. However, the morphologic changes do not unequivocally explain possible metabolic disturbances causing retarded intestinal wound healing.     

The distribution,ontogeny and origin in the rat of Ia-positive cells with dendritic morphology and of Ia antigen in epithelia,with special reference to the intestine

Ia antigens were localized in cryostat sections of rat intestine and other tissues by an indirect immunoperoxidase technique using monoclonal antibodies that recognize the rat antigens homologous to the gene products of the I-A and I-E subregions of the mouse major histocompatibility complex (MHC). Two categories of Ia⁺ cells were characterized, namely epithelial cells and bone marrow-derived cells with dendritic morphology. In the small intestine Ia antigen was present in the distal 2/3 of the absorptive epithelium but absent from the bases of the villi, the crypts and the epithelium covering the Peyer's patches. The distribution in nude rats was similar, indicating that T lymphocytes are not obligatory for its expression. In ontogeny Ia antigen was absent in the epithelium of neonatal gut, appearing at about 4 weeks of age and reaching adult levels at about 6 weeks. Different rat strains showed large differences in the amount of Ia antigen expressed by villus epithelium and the traits for the level of expression were shown to map outside the MHC. The levels of expression of Ia antigen in the proximal tubules of the kidney followed that of the gut epithelium in the different strains and in both tissues was mostly intracellular. Studies with chimeras showed that the Ia antigen in epithelial cells was not acquired from bone marrow-derived cells. The second category of cell studied had a characteristic dendritic morphology and was present in large numbers in the lamina propria of the villi and in the crypts. In the Peyer's patches these cells were present both in the subepithelial dome region and within the epithelium itself. These Ia⁺ dendritic cells were present in nude rat jejunum and appeared in normal fetal gut by 18 days gestation and were also shown to migrate into antigen-free grafts of fetal gut. This suggests that they do not require stimulation from antigens, bacterial products or T lymphocytes in order to localize in the gut or to express Ia antigen. Studies with other cell surface markers suggest that the Ia⁺ cells with dendritic morphology represent a range of cell types, some with similarities to macrophages and others to nonphagocytic dendritic cells.     

The small intestine in experimental diabetes: cellular adaptation in crypts and villi at different longitudinal sites

Intestinal adaptation at the cellular level was examined in groups of streptozotocin-diabetic and agematched control rats. Small intestines were removed and divided into four segments of roughly equal length. For each segment, epithelial volume, villous and microvillous surface areas and the mean volumes of epithelial cells in crypts and villi were estimated. From these data, we were able to estimate total numbers of epithelial cells in crypts and villi, assess adaptation at the level of the average cell and explore variation along the crypt-villus axis, between segments and between groups. Whilst the villus:crypt cell ratio did not change, diabetic animals contained about 80% more epithelial cells than control rats. The morphophenotype of villous epithelial cells (represented by nuclear volume, cell height, area and volume, and number and surface area of microvilli) was basically the same as that in controls. By contrast, crypt cells and their nuclei were 40–50% bigger in diabetic rats. Significant differences between segments were confined to the numbers and sizes of crypt cells and their nuclei. We conclude that experimental diabetes leads to both proliferative and hypertrophic responses within crypts. Crypt cells become fatter but not taller. Crypt hyperplasia is accompanied by an equiproportionate increase in villous epithelial cells, but these are of essentially normal morphophenotype.