Differentiation of crypt epithelium in human palatine tonsils: the microenvironment of crypt epithelium as a lymphoepithelial organ.

The differentiation of the keratinocytes of the human palatine tonsils were studied by means of light and electron microscopy and immunohistochemistry using a polyclonal (K) and two monoclonal antikeratin antibodies (PKK1, PKK2). In the surface epithelium, the basal cells, cuboidal or columnar in shape, undergo progressive terminal differentiation and are transformed into the flattened cells of the upper layers. K reacts with both the basal and spinous layers, while PKK1 and PKK2 mark exclusively the basal layer. In the neck portion of the crypt, cavities containing one or aggregated lymphocytes with amorphous substances are observed in the spinous layer. The cavities are surrounded by elongated cytoplasmic processes of transformed epithelial cells bearing surface microvilli. These transformed epithelial cells display intense PKK1- and PKK2-positive reactions, whereas other conventional polygonal cells in the vicinity remain PKK1- and PKK2-negative as do those in the surface epithelium. In the deep portion of the crypt, where numerous lymphocytes invade the epithelium, the epithelial cells are transformed into star-shaped reticulum cells showing PKK1- and PKK2-positive reactions. The extended and branched cytoplasmic processes interconnect with one another constituting a complex network of reticulum cells, the well known reticulation of the crypt epithelium. Ten-nm filaments are usually oriented parallel to the longitudinal axis of transformed epithelial cells. Our observations suggest that the cell-shape transformation, i.e., from conventional polygonal epithelial cells into epithelial reticulum cells, occurs when the epithelial cells are in close contact with the infiltrating lymphocytes, and that this transformation is accompanied by a change in keratin phenotype.     

Association between keratin staining patterns and the structural and functional aspects of palatine tonsil epithelium.

The keratin composition of stratified squamous epithelia has a complex pattern, which varies in different regions and as a result of pathological developments. The exact factors responsible for the characteristic keratin composition in a given epithelium are unknown. However, the environment, including factors from the connective tissue, is known to influence epithelial morphology and keratin composition. We here report that the reticulated squamous epithelium of the crypts of palatine tonsils shows an extensive staining for keratins 5 and 19 in basal as well as suprabasal cells, in contrast to neighbouring non-reticulated crypt epithelium and the epithelium at the tonsillar surface, in which staining is restricted to basal cells. The reticulation of the crypt epithelium is thought to be initiated by infiltration of immune-related cells in a preexistent non-reticulated epithelium. The extensive staining for keratins 5 and 19 in reticulated crypt epithelium correlates with the presence of numerous immune system-related cells and marked expression of intercellular adhesion molecule-1 (ICAM-1), thought to be involved in inflammatory and immunological responses. The results suggest that the massive lymphocytic traffic in the reticulated crypt epithelium and the overall distinct immune environment are responsible for the unique keratin staining pattern observed.     

大鼠胃肠道5-羟色胺免疫活性内分泌细胞的分布及形态学观察

本文用肠卷石蜡切片的免疫组织化学反应(硫酸镍铵加强的PAP法)对5只大鼠胃肠道的5-羟色胺(5-HT)免疫活性内分泌细胞的分布及形态进行了研究。结果表明,大鼠胃肠道5-HT免疫活性内分泌细胞在胃幽门部、十二指肠和结肠的密度最高,在空肠、回肠、盲肠和直肠密度中等,在胃体部密度最低。5-HT免疫活性内分泌细胞的形状多样。有的细胞有几个突起穿行于其它上皮细胞之间;有的细胞的基底部有突起,突起的末端含有5-HT阳性物质;有时还见突起穿过基膜进入固有层内。多数细胞的5-HT阳性物质释放到腺腔面和肠腔面,说明EC细胞有内、外两种分泌方式释放5-HT。     

Distinct morphology of serotonin-containing enterochromaffin (EC) cells in the rat distal colon

The present study was performed to examine the distribution and distinct morphology of the serotonin-containing enterochromaffin (EC) cells in the rat distal colon by immunohistochemical and electron microscopic methods. Serotonin-immunohistochemistry revealed that most of the serotonin-immunoreactive EC cells possessed extended cytoplasmic processes. In particular, the immunoreactive EC cells with long processes located along the body of the crypt were characterized by their bipolar processes comprising one with the terminal swellings extending vertically down to the basal crypt and the other running up along the luminal side - in many cases, with the apical ends reaching the glandular lumen. Moreover, a few EC cells had long processes which resembled neuronal processes with varicosities. Electron microscopic observations revealed rod-like, tortuous, oval, or round small pleomorphic granules in the long processbearing EC cells. The cell bodies and processes directly faced the crypt epithelial cells - including the enterocytes and goblet cells on one side and the basement membrane on the opposite side. The accumulation of the granules sometimes appeared within the cytoplasm on the side of the epithelial cells. These findings suggest that serotonin is released from the long processes of the EC cells and directly acts in a paracrine fashion on the crypt epithelial cells to secrete electrolytes and fluids into the colonic lumen. The long cytoplasmic processes of the EC cells may be a major contributor to the serotonininduced secretory events in the rat distal colon.     

The bcl-2 proto-oncogene and the gastrointestinal epithelial tumor progression model.

We report overexpression of the proto-oncogene bcl-2 in gastrointestinal adenocarcinoma and its precursor lesions. The bcl-2 proto-oncogene is centrally involved in the oncogenesis of human follicular lymphoma via a chromosomal translocation t(14;18)(q32;q21) and is also expressed in the epithelial regenerative compartment or the basal crypts of the normal colon and small intestine. We describe an immunohistochemical analysis of fixed, paraffin-embedded tissue using both a polyclonal rabbit and a monoclonal mouse antibody to the Bcl-2 protein. In addition to confirming bcl-2 expression in normal colonic and small intestinal crypts, we also observed expression in the gastric epithelial regenerative compartment, the mucous neck region. No increased expression was found in nonneoplastic or inflammatory gastrointestinal conditions, including ulcerative colitis, Crohn's disease, or inflammatory or hamartomatous polyps. Increased bcl-2 expression, however, was present in hyperplastic colonic polyps and in the majority of dysplastic lesions, from the earliest precursors through large adenomas, high grade flat dysplasia, and adenocarcinoma, all in comparison with adjacent internal control normal epithelium. Increased expression was present in dysplastic glandular lesions from all gastrointestinal sites, including colon, small bowel, and stomach. Furthermore, bcl-2 expression was frequently abnormal in nondysplastic epithelium surrounding dysplastic lesions, suggesting that altered expression occurred before the development of morphological dysplasia. Specifically, directly contiguous morphologically nondysplastic epithelium often showed abnormal bcl-2 expression throughout the full length of the crypt-villus axis. This expression pattern gradually diminished to involve only the crypt base (the normal pattern of expression), proceeding away from malignant or dysplastic lesions. Abnormal bcl-2 immunoreactivity in 1), the earliest precursor dysplastic lesions and its persistence throughout neoplastic progression and 2), contiguous morphologically unaltered nondysplastic epithelium suggests that bcl-2 alterations occur early during the morphological and molecular sequence of events leading to gastrointestinal epithelial neoplasia.     

Specialized metaplastic columnar epithelium in Barrett's esophagus. A comparative transmission electron microscopic study

Barrett's esophagus develops as a complication of regurgitant esophagitis and predisposes patients to the development of dysplasia and esophageal adenocarcinoma. Prior ultrastructural studies have suggested that Barrett's epithelium is a mucous secretory epithelium that shares some morphologic features with the intestine. The origin and development of Barrett's epithelium and the cellular abnormalities accompanying its neoplastic progression are poorly understood. In an attempt to better understand the histogenesis of the mucus-producing cells that predominate in Barrett's epithelium, these cells were studied by transmission electron microscopy and compared with other upper gastrointestinal epithelia: esophageal glands, normal gastric surface, pit, and cardiac gland regions, gastric intestinal metaplasia, and normal jejunal villous tip and crypt regions. A total of 134 mucosal biopsies from the stomach and esophagus of 28 patients with Barrett's esophagus and 37 biopsies from 14 other control patients were studied. Barrett's specialized metaplastic surface cells display a spectrum of ultrastructural features among three main surface columnar epithelial cell types: mucous cells resembling those seen in the normal gastric surface epithelium or resembling mucous neck cells normally seen in the gastric pits; goblet cells similar to those seen in the jejunum; and "pseudoabsorptive" cells with features of both gastric mucous secretory cells and jejunal absorptive cells. Cytoplasmic organelles of Barrett's specialized metaplastic, normal gastric mucous neck, and normal gastric surface mucous epithelial cells, including rough endoplasmic reticulum, glycogen aggregates, Golgi apparatus, and mucous secretory granules, have common ultrastructural features associated with mucus synthesis. The morphologic heterogeneity of Barrett's specialized metaplastic cells and common ultrastructural features associated with normal mucus biosynthesis suggest that they develop from a gastrointestinal stem cell that retains the capacity for a wide range of normal and abnormal differentiation in the esophagus. The identity of this undifferentiated cell, which may reside in normal proximal gastric or esophageal mucosa, remains unknown. However, the gastric mucous neck cell has properties that suggest it could be the progenitor cell for Barrett's esophagus because it is a stem cell that has ultrastructural similarities to Barrett's specialized metaplastic epithelial cells and it is located in intact gastric mucosa adjacent to where Barrett's esophagus forms.     

The ultrastructure of the crevicular epithelium of cat gingiva

The ultrastructure of the crevicular epithelium of clinically healthy cat gingiva was similar to that of other non-keratinizing oral epithelia. However, it differed in that the intercellular spaces were wide and extended as a continuous network from the basal lamina to the epithelial surface. Basal cells contained numerous mitochondria, Golgi apparatus, free ribosomes and a fine feltwork of evenly distributed tonofilaments. Hemidesmosomes were present in relation to the basal lamina. Cells in the intermediate layers showed a decrease in the number of organelles and an increase in concentration of tonofilaments, Superficial cells were further flattened and the remaining organelles commonly showed degenerative changes. Epithelial cells showed prominent microvilli extending into the intercellular spaces. Some of these formed desmosomes with similar processes of adjacent cells. Occasional randomly distributed tight junctions were also observed. Inactive basal melanocytes, more superficial Langerhans cells and leucocytes were seen between epithelial cells. The great majority of leucocytes were neutrophils and many of these ruptured as they approached the epithelial surface scattering their specific granules into the intercellular spaces. These findings are discussed in relation to the peculiar permeability of the gingival crevicular region of the oral mucosa to tissue fluid and leucocytes.     

'Senescence-associated' beta-galactosidase activity in the upper gastrointestinal tract

Beta-galactosidase activity at pH 6 is associated in vitro with senescence and cellular death, but in vivo data are sparse. This study undertook firstly to map 'senescence-associated' beta-galactosidase activity (SAbetaG) at pH 6 in normal epithelia and mucosae of the upper gastrointestinal tract. As escape from senescence confers a proliferative advantage, a reduction in SAbetaG activity might be predicted in neoplasia and their precursors in vivo. This prediction was tested in metaplastic, dysplastic, and neoplastic epithelium of the upper gastrointestinal tract. Histochemical staining for SAbetaG was performed at pH 6 on cryostat sections of 350 endoscopic biopsies from sites including oesophagus, stomach, and duodenum of 46 patients: 28 with Barrett's oesophagus (two with adenocarcinoma), 15 with gastric adenocarcinoma, and three with oesophageal squamous cancer. A staining score (range 0-6) was assigned to epithelial cells in all mucosae and scores were calculated for surface (luminal), intermediate, and deep (basal) layers. The strongest SAbetaG activity was in surface luminal cells of normal duodenal mucosa (mean score 3.6+/-0.5; n=19), 'specialized' Barrett's mucosa (mean 2.2+/-0.12; n=105), and intestinal metaplasia in the stomach (mean 2.4+/-0.40; n=16). Squamous epithelium was consistently negative for SAbetaG activity. Low- and high-grade Barrett's dysplasia showed no decrease in SAbetaG activity, but reduced activity was seen in gastric and oesophageal adenocarcinomas (mean 1.24+/-0.29; n=17; p=0.012). In six gastric adenocarcinomas, there was no detectable activity. Whether SAbetaG is truly a marker of cellular senescence in vivo remains to be determined. Activity is low in mucosal proliferation compartments and increases with cellular differentiation, especially in native or metaplastic intestinal mucosae. SAbetaG activity persists in dysplastic mucosae but may show some reduction or loss in adenocarcinomas (p=0.0012). Loss of SAbetaG activity is not, therefore, an early event in glandular dysplasia-neoplasia of the upper gastrointestinal tract.     

Three-dimensional scanning electron microscopic study of the normal hamster olfactory epithelium

Summary The olfactory epithelium of the adult hamster (Mesocricetus auratus) was studied using the scanning electron microscope. A method that produced fractures in the epithelium exposed structures below the surface and made it possible to examine the morphological and structural relationships among cells.Three cell types were studied: supporting cells, olfactory neurons (receptor cells) and basal cells. Supporting cells were observed spanning the full extent of the epithelium, and had basal foot processes that terminated at or near the basal lamina. Along the lateral margin of supporting cells, cellular processes were observed extending outwards, reaching olfactory neurons and adjacent supporting cells. These cellular contacts among supporting cells and olfactory neurons were present at different levels of the epithelium. Olfactory neurons were located primarily in the middle and lower epithelial regions. Their dendritic processes reached the epithelial surface in a straight or tortuous manner, passing between the supporting cells. Olfactory axons were observed as thin unbranched processes that emerged from a conical hillock region, passed basally, and fasciculated into larger sensory bundles within the lamina propria. Basal cells were observed adjacent to the basal lamina as a row of single cells or clustered in groups. Within the lamina propria connective tissue, blood vessels, axon bundles and Bowman's glands were examined. Bowman's glands were composed of pyramidal secretory cells arranged about a single duct that extended to the epithelial surface.Scanning electron microscopy provided a unique three-dimensional analysis of cell structure within the olfactory epithelium. The results provide new and different observations on the detailed morphology and intimate relationships that exist among epithelial cells, and complement previous light and transmission EM observations.     

Histochemical similarities of mucins produced by Brunner's glands and pyloric glands: A comparative study

Mucins of the gastroduodenal junction are secreted by the mucous surface and mucus-producing glandular cells in the stomach, and by goblet cells and Brunner's glands in the duodenum. Developmental studies have demonstrated that Brunner's glands can arise from undifferentiated gastric epithelium and/or intestinal epithelium in the proximal duodenum. The aim of this study was to investigate the carbohydrate composition of mucins from this region and compare it with that of mucins from Brunner's glands to evaluate the probable evolution of mucins from these glands. Toward that end, paraffin sections from 13 mammalian species were stained by classic carbohydrate histochemistry and treated with 13 lectins. In general, the mucous surface cells of the stomach, pyloric glands, duodenal goblet cells, and Brunner's glands secretory epithelium had different lectin-binding patterns. However, the lectin-binding profile of the secretory epithelium of Brunner's glands resembled that of pyloric glands more closely than that of duodenal goblet cells and mucous surface cells of the stomach. Mucins from Brunner's glands and pyloric glands showed a greater terminal carbohydrate residue diversity than those of gastric mucous surface cells or duodenal goblet cells. The lectin-binding profile argues for the evolution of similar mucins from the epithelia of Brunner's glands and pyloric glands. The greater diversity of carbohydrate residues in mucins secreted by Brunner's glands suggests that their mucus is more adaptable. This may explain why Brunner's glands metaplasia rather than goblet cell metaplasia is seen in the mucosa adjacent to chronic intestinal ulcers.     

An immunohistochemical study of cellular and nervous elements in the taste organ of the bullfrog, Rana catesbeiana

The cellular and nervous elements of the bullfrog taste organ were examined by immunohistochemical methods using various antibodies. The immunoreactivity for spot 35 protein, a soluble protein isolated from bovine cerebellum, was found in numerous taste cells located at the middle or slightly lower levels within the gustatory cell layer. The immunoreactive cells possessed cytoplasmic processes rising upward the free surface and also issued branched processes to the base of the epithelium. The immunoreaction for spot 35 protein was found diffusely throughout the cytoplasm from the apical to the basal parts of the taste cells. NSE-immunoreactive taste cells were located at the upper or middle levels within the gustatory cell layer in the taste organ. The fact that the cells were smaller in number and size than spot 35 protein-reactive cells and further differed in localization distinguished the NSE-taste cells from the spot 35 protein cells. Serotonin-like immunoreactivity was detectable in the basal cells localized at the base of the taste epithelium. The immunoreactive cells were arranged in a circle at the periphery of the taste organ, each extending a slender process toward the center. The terminal portion of this process spread leaf-like; numerous fine projections protruded from its margin. The serotonin-immunoreactive cells appear to coincide with the monoamine-containing basal cells, which have been previously reported. Substance P-, calcitonin gene-related peptide (CGRP)-, vasoactive intestinal polypeptide (VIP)-, peptide HI (PHI)- or gastrin releasing peptide (GRP)-immunoreactive nerve fibers with varicosities were demonstrated within the taste organ. Some substance P-fibers ran along the bottom of the taste organ epithelium. A few thinner substance P-fibers ascended among the epithelial cells of the organ and terminated closely below the free surface. CGRP-fibers were found to correspond to substance P-fibers from their evidencing a double immunostaining. VIP- and PHI-fibers formed a meshwork in the basal area of the taste epithelium. Abundant substance P- and/or CGRP-fibers formed a meshwork among the ciliated cells located at the periphery of the taste organ. However, PHI- and GRP-fibers were detected less than substance P- and/or CGRP-fibers, though VIP-fibers were rarely present in the same region. Neurofilament protein- or tyrosine hydroxylase-like immunoreactivities were found in thick nerve fibers in the taste organ, whereas no immunoreactivities were present in cellular elements within the taste organ. The relationship between cellular and nervous elements in the taste organ was examined by double immunostainings.(ABSTRACT TRUNCATED AT 400 WORDS)     

Morphology of the buccopharyngeal portion of the gill in the fathead minnow Pimephales promelas (Rafinesque)

Buccopharyngeal epithelium covering gill arches and gill rakers of the fathead minnow was studied by light microscopic, scanning, and transmission electron microscopic techniques. Mature mucous cells in goblet pattern and nonmucus containing cells were in the apical one-third of the tissue. The latter cells contributed to a surface microridge system which overlapped apices of goblet cells. The bottom of the epithelium was comprised of a continuous row of darkly stained basal epithelial cells. In this region, two to three epithelial cells of similar staining characteristics were piled up forming apical columns which partially encircled nests of lightly stained cells. A basal lamina and thick basement lamella of about 20 plies of orthogonally arranged collagen supported the epithelium. Numerous taste buds were seen in gill arches and rakers. Taste bud cellular components included marginal cells, light receptor cells, dark receptor cells, and basal cells. These were identical in all taste buds. Taste bud surface morphology differed between gill arch and raker. Pores of the former were depressed, while those of the latter were raised. Thick microvilli of taste pores were apical extensions of light cells, while smaller, more numerous microvilli were projections from dark cells.     

Electron microscopy of intestinal adenomatosis in the blue fox, Alopex lagopus

Scanning electron microscopy of adenomatous intestinal tissue in the blue fox revealed an irregular surface topography of the colon with increased diameter of the crypt openings and prominent ridge formations between crypts. The ileum showed villous atrophy and fusion. Microvilli were short and irregular. Small ulcerations of intestinal mucosa were seen. Freeze-fracture revealed curved intracellular organisms in the altered epithelial cells. Transmission electron microscopy showed features associated with immaturity and high protein synthesis. Filamentous extensions from the basolateral plasma membrane of altered epithelial cells sometimes penetrated the basal lamina. The cytoplasm contained numerous polyribosomes, nuclei had many indentations and large and irregular nucleoli. Intracellular bacteria, with morphology corresponding to Campylobacter spp. were found in the apical epithelial cytoplasm. No host-cell-derived membrane was seen to surround the bacteria.     

Ultrastructural study of postnatal development of the tonsillar crypt epithelium of the musk shrew, Suncus murinus

Summary An ultrastructural study was made of the postnatal development of the tonsillar crypt epithelium in the musk shrew, Suncus murinus. On day 3 after birth, a particular kind of large lymphoid cell was first seen to move through the basement membrane into the epithelium. The next migration was that of lymphocytes, which passed through holes in the basement membrane. On days 5 to 7, the lymphocytes formed clusters, and pale epithelial cells of low electron density appeared. The cell clusters and pale epithelial cells fused on day 10. By day 14, these epithelial cells extended cytoplasmic projections to the surface of the epithelium, which had many heterophagic vacuoles and some microvilli-like structures. These findings suggest that the lymphoepithelial relationship is important for the organization of the immunological microenvironment in tonsillar crypt epithelium of the neonatal musk shrew.     

Brunner's glands of the duckbilled platypus (Ornithorhynchus anatinus)

Brunner's glands in the platypus form a lobulated, glandular collar confined to the submucosa of the most distal portion of the stomach. The glands end immediately proximal to the gastrointestinal junction and excretory ducts empty in the region where the stratified squamous epithelium lining the stomach changes abruptly to the intestinal lining epithelium of the duodenum. An individual gland of Brunner is composed of several elongate lobules drained by intralobular ducts which often join to form a single excretory duct. Light and electron microscopic studies have shown the secretory tubules to be comprised of large, pyramidal cells limited basally by a delicate basal lamina. The ergastoplasm, cisternae of which are dilated and contain amorphous material, is associated with numerous ribosomes. In basal and perinuclear regions intercisternal granules and smooth surfaced vesicles are found. Numerous small vesicles found in supranuclear areas apparently form from the smooth membrane portions of ergastoplasm located adjacent to Golgi complexes. Membrane-bound amorphous granules of varying electron density occupy the apical cytoplasm and show a tendency to coalesce before emptying their contents into the adjacent lumen. The intralobular duct system is lined initially by a columnar epithelium which changes to a simple squamous form before the ducts combine to form a short excretory duct lined by stratified squamous epithelium. The epithelium lining the duct system contains relatively few organelles but appears to be engaged in a limited amount of synthesis and release of secretory material. Histochemical studies indicate that both the secretory tubules and the duct system elaborate a neutral mucopolysaccharide.     

Dedifferentiation of iris epithelium during lens regeneration in newt larvae

Early stages in lens regeneration from the pigmented epithelium of the dorsal iris were studied in larval Notophthaimus viridescens by means of transmission electron microscopy. Normal iris epithelium is composed of two layers of low cuboidal cells, packed with melanosomes and surrounded by a basal lamina. Scattered desmosomes attach adjacent cells. Following lens removal, the intercellular spaces enlarge and the epithelial cells increase in size. Some irregular microvilli from these cells extend into the intercellular spaces. Macrophages invade the iris epithelium and phagocytize melanosomes discharged from the pigmented cells. These invading macrophages have numerous microprojections and are often separated from the surface by a very thin layer of iris epithelial cell cytoplasm. In the iris cells, nucleoli become more prominent and granular, polyribosomes increase greatly in number, melanosomes gradually disappear, mitochondria become more numerous, and mitotic activity is greatly augmented. Fine cell processes of adjacent cells interdigitate near the external surface, where numerous micropinocytotic vesicles can be seen. Over the external surface, the basal lamina may be disrupted or duplicated in places where pseudopodia project from iris cells or a macrophage has entered an intercellular space. It is lacking on the lumenal surface. Sloughed membranes are often found in these intercellular spaces.     

Polymeric IgA is Complexed with Secretory Component (SC) on the Surface of Human Intestinal Epithelial Cells

Viable suspensions of columnar cells were obtained from the surface and outer crypt epithelium of human colon mucosa by a combined treatment with citrate and EDTA solutions and mechanical disruption, but without the use of enzymes. A substantial fraction of the isolated cells contained free SC and secretory IgA in a cytoplasmic distribution that corresponded to previously reported immunohistochemical and immunoelectron-microscopical results obtained with tissue sections. On their surface the same cells were shown to bear SC complexed with J-chain-containing polymeric IgA, whereas only occasional traces of free SC were found. IgM was detected in the surface patches which contained the largest concentrations of SC and IgA. These findings demonstrate that in SC-producing epithelial cells SC molecules become exposed on the plasma membrane, thereby being able to bind specifically J-chain-containing IgA and IgM present in the tissue fluid. Such adsorptive complexing is probably a prerequisite for the selective pinocytotic transport of these two Ig classes through glandular epithelium in man.     

Lysozyme localization in normal and diseased human gastric and colonic mucosa. A correlative histochemical, immunohistochemical and immunoelectron microscopic investigation.

The distribution of lysozyme in normal and pathological human gastric and colonic mucosa was studied by light and electron microscopic immunocytochemical techniques and compared with histological and histochemical features. Lysozyme was localized in pyloric glandular epithelial cells, mucous neck cells of fundic glands, Paneth cells and some crypt cells of the mature colonic mucosa. In addition, lysozyme was detected in a large spectrum of "immature" or "regenerative" epithelium: neck cells of the gastric regenerative zone, undifferentiated columnar cells of surface and hyperplastic interfoveolar crests of the stomach, regenerative cells in a healed gastric ulcer, some goblet cells in incomplete intestinal metaplasia, cells of the regenerative zone at the bottom of colonic crypts and, finally, fetal intestinal epithelium. Electron microscopically, we localized lysozyme in the central core of mucous granules in the pyloric gastric glandular epithelium and in the dense mucous granules in gastric mucous neck cells. Lysozyme was also detected in some immature mucin-producing cells of the gastric regenerative zone and in the rough endoplasmic reticulum of surface hyperplastic columnar gastric cells. At the electron microscopic level, a peculiar correlation between the immunopattern of lysozyme and the morphology of mucous granules has been postulated. All our data support and extend the view that the presence of lysozyme may be related to cell immaturity as well as to a regenerative state of the cell. Finally, the lysozyme distribution and its relation to mucosubstances in gastric and colonic carcinoma suggest that lysozyme should not be considered an exclusive marker of cells of gastric derivation.