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Identification of bovine trophoblast protein-1, a secretory protein immunologically related to ovine trophoblast protein-1.

This paper demonstrates that a group of proteins, representing a major secretory component of cattle conceptuses, is immunologically related to ovine trophoblast protein-1 (oTP-1), a principal product of culture Day 13 to 21 sheep conceptuses. Conceptuses from cows (Day 17-18) and ewes (Day 16-17) were cultured for 24 h in the presence of L-[3H]leucine. By using a rabbit antiserum to oTP-1 and Ouchterlony double-immunodiffusion analysis it was shown that material in the bovine conceptus culture medium was serologically related, but not identical, to oTP-1. A solid-phase radiobinding assay indicated that the cross-reacting bovine secretory component had an affinity for anti-oTP-1 antibody similar to that of oTP-1. Anti-oTP-1 antiserum specifically immunoprecipitated a group of 6-8 polypeptides from culture medium of cow conceptuses which, when analysed by two-dimensional gel electrophoresis, fell into two major molecular weight classes (22,000 and 24,000) with isoelectric points between 6.5 and 6.7. These immunoprecipitated polypeptides, defined as bTP-1, constituted the major secretory products of Day 16-25 cow conceptuses. They were larger and more basic than oTP-1 polypeptides (Mr about 18,000; pI 5.4-5.7). Anti-oTP-1 antiserum also recognized the major translation product of Day 17 bovine conceptus mRNA, a polypeptide significantly smaller (Mr approximately 18,000) than the secreted protein. It is suggested that oTP-1 and the homologous bovine protein may play similar roles in the phenomenon of maternal recognition of pregnancy in the two species.

Animals↗

Heterogeneity of expression of IgA receptors by human, mouse, and rat eosinophils.

IgA is the most abundant class of Abs at mucosal surfaces where eosinophils carry out many of their effector functions. Most of the known IgA-mediated functions require interactions with IgA receptors, six of which have been identified in humans. These include the IgA FcR FcalphaRI/CD89 and the receptor for the secretory component, already identified on human eosinophils, the polymeric IgR, the Fcalpha/muR, asialoglycoprotein (ASGP)-R, and transferrin (Tf)R/CD71. In rodents, the existence of IgA receptors on mouse and rat eosinophils remains unclear. We have compared the expression and function of IgA receptors by human, rat, and mouse eosinophils. Our results show that human eosinophils express functional polymeric IgR, ASGP-R, and TfR, in addition to CD89 and the receptor for the secretory component, and that IgA receptors are expressed by rodent eosinophils. Indeed, mouse eosinophils expressed only TfR, whereas rat eosinophils expressed ASGP-R and CD89 mRNA. These results provide a molecular basis for the differences observed between human, rat, and mouse regarding IgA-mediated immunity.

Animals↗

The three genes lipB, lipC, and lipD involved in the extracellular secretion of the Serratia marcescens lipase which lacks an N-terminal signal peptide.

The extracellular lipase of Serratia marcescens Sr41, lacking a typical N-terminal signal sequence, is secreted via a signal peptide-independent pathway. The 20-kb SacI DNA fragment which allowed the extracellular lipase secretion was cloned from S. marcescens by selection of a phenotype conferring the extracellular lipase activity on the Escherichia coli cells. The subcloned 6.5-kb EcoRV fragment was revealed to contain three open reading frames which are composed of 588, 443, and 437 amino acid residues constituting an operon (lipBCD). Comparisons of the deduced amino acid sequences of the lipB, lipC, and lipD genes with those of the Erwinia chrysanthemi prtDEC, prtEEC, and prtFEC genes encoding the secretion apparatus of the E. chrysanthemi protease showed 55, 46, and 42% identity, respectively. The products of the lipB and lipC genes were 54 and 45% identical to the S. marcescens hasD and hasE gene products, respectively, which were secretory components for the S. marcescens heme-binding protein and metalloprotease. In the E. coli DH5 cells, all three lipBCD genes were essential for the extracellular secretion of both S. marcescens lipase and metalloprotease proteins, both of which lack an N-terminal signal sequence and are secreted via a signal-independent pathway. Although the function of the lipD gene seemed to be analogous to those of the prtFEC and tolC genes encoding third secretory components of ABC transporters, the E. coli TolC protein, which was functional for the S. marcescens Has system, could not replace LipD in the LipB-LipC-LipD transporter reconstituted in E. coli. These results indicated that these three proteins are components of the device which allows extracellular secretion of the extracellular proteins of S. marcescens and that their style is similar to that of the PrtDEF(EC) system.

Amino Acid Sequence↗

Xenografting of normal colonic mucosa in athymic mice.

Colonic mucosa was implanted subcutaneously into nude mice in order to investigate the potential use of xenografts as an in vivo model system for the study of colonic epithelial proliferation and differentiation. The xenografts were followed for 5 weeks. Proliferation was studied by bromodeoxyuridine (BrdU) incorporation followed by visualization of the DNA-synthesizing cells with an anti BrdU monoclonal antibody. Differentiated cells were visualized by histochemical staining of goblet- and enterochromaffin cells and of columnar cells by immunoperoxidase staining for carcinoembryonic antigen (CEA), secretory component, and serotonin. In different strains of mice different observations were made. Less immunocompetent strains (Balb c nu/nu, NMRI nu/nu) developed abscesses at the site of the xenograft as well as wasting disease. These phenomena almost never occurred in CD-1 nu/nu mice. The success rate was highest in CD-1 nu/nu mice. After about 1 week, only crypt base cells remained vital and started to repopulate crypts with epithelial cells showing normal colonic differentiation features such as CEA, secretory component, and serotonin immunoreactivity and mainly sulphomucin production. After longer periods of time, crypts started to form cyst-like structures due to accumulation of secretion products and dead cells. DNA-synthesizing cells were seen in the basal areas of recognizable crypts and in the cyst-like structures in a random distribution. These results indicate that normal colon mucosa xenografted into nude mice maintains its proliferative and differentiating capacity for at least 5 weeks.

Animals↗

Inflammatory bronchopulmonary response of preterm infants with microbial colonisation of the airways at birth.

The inflammatory indicators in the tracheobronchial aspirate (TA) of 81 ventilated preterm infants with microbial colonisation of the airways and in non-colonised neonates were analysed on the first day of life. TA was assessed for chemotactic activity, neutrophil cell count, and concentrations of leukotriene B4, C5a, interleukin-1, interleukin-8, elastase-alpha 1-proteinase inhibitor, free elastase and albumin. Concentrations of mediators were related to concentrations of the secretory component of IgA. The infants' gestational age was mean (SD) 27.9 (2.0) weeks, birthweight 945 (179) g. In 12 infants (15%) microbial colonisation of the airways was present (Ureaplasma urealyticum n = 7; bacteria n = 5). Compared with non-colonised neonates (n = 69), chemotactic activity, neutrophil count, and concentrations of interleukin-1, leukotriene B4 and elastase-alpha 1-proteinase inhibitor were significantly higher in the colonised group. The difference was most pronounced for IL-1 concentrations, both with and without correction for secretory component. There was also a trend towards increased concentrations of interleukin-8 in the latter group. There were no differences for concentrations of C5a and albumin in the TA of both groups. It is concluded that airway colonisation with U urealyticum or bacteria at birth is associated with a clinically relevant bronchopulmonary inflammatory response. Increased concentrations of interleukin-1 in TA on the first day of life may be a marker of perinatal colonisation of the airways.

Bacterial Infections↗

[Quantitative determination of immunoglobulins in serum and saliva of patients with denture stomatitis].

A quantitative study on the immunoglobulins G, M, and A in serum and saliva was performed as well as of secretory immunoglobulin A and of the secretory component in the saliva of 35 patients with prosthetic stomatitis and 30 healthy controls without prostheses. The method of radial immune-diffusion in agar according to Mancini, modification of G. Stankova et al. (1983) was used. The study established that there was no statistically significant difference (p greater than 0.05) in the values of immunoglobulins G, M and A in the sera of the subjects from both groups. Statistically significant increase (p less than 0.001) of the values of the immunoglobulin A, secretory immunoglobulin A and secretory component was established in the saliva of the patients with prosthetic stomatitis as compared with the same values in the control group, very likely due to the local reaction of saliva to the present prosthetic constructions.

Adult↗

Mucosal immune responses to meningococcal group C conjugate and group A and C polysaccharide vaccines in adolescents.

Previous studies in children have shown that Haemophilus influenzae type b (Hib) polysaccharide conjugate vaccines can reduce nasopharyngeal carriage of H. influenzae and provide herd immunity and suggest that this effect is mediated through mucosal antibodies. As this phenomenon may operate in other invasive bacterial infections which are propagated by nasopharyngeal carriage, mucosal antibody responses to meningococcal C conjugate and A/C polysaccharide vaccines were investigated. A total of 106 school children aged 11 to 17 years were randomized to receive a single dose of either conjugate or polysaccharide vaccine in an observer-blind study. Before and at 1, 6, and 12 months after immunization, samples of unstimulated saliva were collected and assayed by enzyme-linked immunosorbent assay for group C polysaccharide-specific immunoglobulin A (IgA), IgA1, IgA2 and secretory component, IgG antibodies, and total IgG and IgA. A subset of serum samples were also assayed for specific IgA and IgG antibodies. The concentrations of specific IgA and IgG in saliva were expressed both as nanograms per milliliter and as nanograms per microgram of total IgA or IgG. One month after immunization, significant increases in antibody titers (both IgA and IgG) were observed in saliva in both groups. There were significant subsequent falls in antibody titers by 6 months. Anti-meningococcal C-specific secretory component and IgA antibody titers were closely correlated (r = 0.85, P < 0.001), but there was no significant correlation between salivary and serum IgA titers, suggesting that IgA antibodies are locally produced. Significant correlation was found between salivary and serum IgG titers (r = 0.52, P < 0.01), suggesting that salivary IgG may be serum derived. Compared with polysaccharide vaccine, the conjugate vaccine induced significantly higher salivary IgG responses (P < 0.05), although there were no significant differences between salivary IgA responses to the two vaccines. The conjugate vaccine induced greater salivary IgG responses than a polysaccharide vaccine. Both vaccines induced significant salivary IgA antibodies. Further studies are needed to establish the functional significance of these mucosal responses.

Adolescent↗

Transmission of IgA and IgG monoclonal antibodies to mucosal fluids following intranasal or parenteral delivery.

BACKGROUND: The efficacy by which passive antibodies can reach the lungs could be important for the outcome of immunotherapy of respiratory pulmonary infections. We examined how transmission to a number of mucosal sites is affected by the route of inoculation. METHODS: Transmission of newly raised IgA class Mabs against mycobacterial surface antigens to saliva, lung or vaginal lavage, bile and serum of BALB/c mice was compared with existing IgG Mabs. ELISA was used for testing body fluids obtained 1-24 h after intranasal or intravenous inoculation and 1-7 days following back-pack tumour growth of hybridomas. RESULTS: Intranasal inoculation resulted in a rapid rise and high levels of both IgA and IgG class Mabs in lung lavage. In contrast, following intravenous Mab injection or back-pack tumour growth of hybridoma cells, effective lung transmission was observed for the IgG1 and IgG2b MAbs, but not for the IgA Mabs. The secretory component was acquired by the transmitted IgA MAbs in the mucosal fluids, but not in the serum. Nevertheless, the time course of mucosal IgA antibody levels was similar to that of the tested IgG Mabs. Furthermore, the relative proportion of transmission to saliva and bile varied between individual Mabs indicating a role of tissue-specific, immunoglobulin class-unrelated mechanisms. CONCLUSIONS: Intranasal, rather than parenteral inoculation of mice is required for the efficient delivery of IgA antibodies against respiratory pulmonary pathogens. Interestingly, IgA-secretory component complexing of intranasally applied Mabs did not significantly influence their persistence in the lungs.

Administration, Intranasal↗

[Action of an anti-inflammatory agent on the nasal mucosa].

The histological integrity of the nasal mucosa assures full efficacy of the respiratory, conditioning and defense functions. Together with ciliated and goblet cells, the respiratory epithelium not only carries out mucociliary clearance but it is also responsible for correct assembly of secretory IgA, the foundation of the mucosal defense system. The secretory component stabilizing the immunoglobulin molecule is indeed, an epithelial glycoprotein which begins to fail when the mucous trophism is altered through inflammatory processes of various natures. The efficacy of an anti-inflammatory drug (tiaprofenic acid) can thus be proven not only because the respiratory and mucociliary transport functions are normalized but, histologically speaking, through an accumulation of IgA in the epithelial cells and nasal secretions as well. In the present experiment the effect of tiaprofenic acid on the local production of antibodies appears prompt and long lasting. On the contrary, respiratory function and mucocillary transport are more deeply affected by structural alterations of the epithelium, most likely because the histological integrity-demonstrated by the increase of IgA in the secretion and accumulation of the secretory component in the epithelium-is the starting point for a perfect coordination according to fixed biological rhythms of all nasal functions.

Adult↗

Human colostral cells. I. Separation and characterization.

Analyses of the cells present in human colostrum obtained from fifty-four healthy donors during the first four days of lactation revealed that there were 3.3 x 10(6) (range 1.1 x 10(5)--1.2 x 10(7)) cells per ml of colostrum. Based on histochemical examinations, it was found that this population consisted of 30--47% macrophages, 40--60% polymorphonuclear leucocytes, 5.2--8.9% lymphocytes, and 1.3--2.8% colostral corpuscles; epithelial cells were rarely encountered. The identity of various cell types was confirmed by Wright's stain and by a series of histochemical techniques which disclosed the presence of non-specific esterase, peroxidase, and lipids. For further characterization, the different types of cells were separated by various methods, such as Ficoll-Hypaque density centrifugation, isokinetic centrifugation on a linear Ficoll gradient, adherence to glass or plastic, and phagocytosis of carbonyl iron. Immunohistochemical staining with FITC- and/or TRITC-labelled reagents to IgA, IgM, IgG, K- and lambda-chains, secretory component, lactoferrin, and alpha-lactalbumin were applied to unseparated as well as separated colostral cells. Polymorphonuclear leucocytes (staining for peroxidase) as well as macrophages and colostral corpuscles (staining for non-specific esterase) exhibited numerous intracellular vesicles that contained lipids as well as various combinations of milk proteins. Lymphoid cells did not stain with any of these reagents and plasma cells were not detected among the colostral cells. Individual phagocytic cells contained immunoglobulins of the IgA and IgM classes, both K and lambda light chains, secretory component, lactoferrin, and alpha-lactalbumin. The coincidental appearance of these proteins in single, phagocytic cells but not in lymphoid cells indicate that the cells acquired these proteins by ingestion from the environment. Markers commonly used for the identification of B lymphocytes (surface immunoglobulins) and T lymphocytes (receptors for sheep red blood cells) were unreliable for the analysis of colostral cells (unless accompanied by subsequent morphological characterization) because strong fluorescence was observed on the surface of many non-lymphoid cells and because numerous macrophages and colostral corpuscles formed rosettes with sheep red blood cells (SRBC). Lymphocytes, often found in association with colostral macrophages or corpuscles, were classified as T cells.

Cell Count↗

Detection of anti-SS-A/Ro and anti-SS-B/La antibodies of IgA and IgG isotypes in saliva and sera of patients with Sjögren's syndrome.

To assess the frequency and the possibility of local production of autoantibodies against SS-A/Ro and SS-B/La in patients with primary Sjögren's syndrome (SS), serum and saliva samples were obtained from 42 patients with SS, 10 with rheumatoid arthritis without sicca syndrome, and 12 healthy volunteers. Autoantibodies were detected using enzyme-linked immunosorbent assay and immunoblotting. The frequencies of IgA anti-SS-A antibody, IgA anti-SS-B antibody, IgG anti-SS-A antibody and IgG anti-SS-B antibody in serum from SS patients were 45%, 50%, 43% and 21%, respectively. The frequencies of IgA anti-SS-A antibody, IgA anti-SS-B antibody, IgG anti-SS-A antibody and IgG anti-SS-B antibody in saliva from SS patients were 31%, 33%, 40%, and 19%, respectively. We also found secretory IgA anti-SS-A and anti-SS-B antibodies accompanying secretory components in saliva and sera in representative SS patients. Significant correlations were found between serum and salivary levels of IgA anti-SS-A antibodies, and between serum and salivary levels of IgA anti-SS-B antibodies in SS patients. Significant correlations were also found between serum and salivary levels of IgG anti-SS-A antibodies, and between serum and salivary levels of IgG anti-SS-B antibodies in SS patients. Immunoblot analysis confirmed the presence of IgA-class autoantibodies against SS-A and SS-B in saliva and serum from representative patients. The presence of IgA- and IgG-class autoantibodies against SS-A and SS-B and those accompanying secretory components in saliva from SS patients suggests the local production of these antibodies and the relationship between local and systemic antibody responses.

Adult↗

Plant expression of chicken secretory antibodies derived from combinatorial libraries.

Delivery of secretory IgA antibodies (sIgA) to mucosal surfaces is a promising strategy to passively prevent infectious diseases. Plants have been proposed as biofactories for such complex immunoglobulin molecules. Recently, the molecular characterization of all four monomers of chicken sIgA (IgA immunoglobulin heavy and light chains, J-chain and secretory component) has been completed, allowing recombinant, up scaled production of chicken sIgA and extension of passive immune strategies to poultry. To test the suitability of the plant cell factory for bulk production of chicken sIgA, we studied the expression of chicken IgA, dIgA and sIgA in planta. To that end, new cassettes were designed that allowed the grafting of immunoglobulin variable regions derived from combinatorial libraries into full-size chicken IgA frames ready for plant expression. Using this system, 10 individual phage display clones, which had previously been selected against Eimeria acervulina antigens, were transferred "from phage to plant". Plant-made chicken antibodies showed strong differences in expression levels, which seemed governed mainly by the stability of their respective light chains. Finally, with the co-expression of chicken IgA heavy and light chains, J-chain and secretory component in N. benthamiana leaves we showed that plant cells are suitable biofactories for the production of assembled chicken sIgA complexes.

Animals↗

Local immunological response in the vagina, cervix and endometrium.

The mechanism of the local excretion of secretory IgA (SIgA) in exocrine secretions has been reviewed. Numerous local IgA-plasma cells, in the lamina propria of the glandular mucosa, synthesize dimeric IgA with J-chain. Free secretory component (FSC) is synthesized and accumulated in the Golgi area of the columnar epithelial cells. It is then supposed to get onto their cell membranes. Dimeric IgA (and some IgM) reaches tn dimeric IgA (and some IgM) and the FSC located in the cell-membrane, whereby SIgA is formed. The complex becomes mobilized and is transported toward the apical part of the cell, where it will be excreted into the mucous coat covering the epithelium. In the female genital tract, the cervical mucosa appears to be better adapted to achieve a local secretory immune system. The endometrium seems less suitable, being normally short of local plasma cells. The vaginal wall appears almost incompatible with the proposed mechanism of local antibody secretion. Criteria for establishing a local immune response in the female genital tract comprise: 1) a lack of correlation between antibody titers in secretions and serum; 2) the demonstration that the secretory antibodies are mainly of IgA class and 3) that they are SIgA molecules, possessing bound secretory component. However, the best criterion would be 4) the observation that antibody is actually synthesized in samples of mucosa, by in vitro culture or immunohistology. Reviewing the literature, relatively few examples were found where SIgA antibodies were demonstrated, and unambiguous evidence for their local synthesis is almost non-existent. In addition, the authors were unable to detect antibody-containing cells in cervical and endometrial biopsies of women locally "immunized" with horse spleen ferritin and bovine serum albumin. The need for further investigation with simple antigens and adequate immunological reagents is stressed.

Antibody Formation↗

Electrophoresis combined with immunologic identification of human tear proteins.

The protein content of normal human tears from five subjects was examined by molecular weight separation using SDS-polyacrylamide gel electrophoresis (PAGE) and by charge separation using agarose isoelectric focusing (IEF) gels. After separation, specific proteins were identified by immunoblot and immunofixation. Tear proteins examined included albumin, IgA, IgG, prealbumin, lactoferrin, lysozyme, secretory component and transferrin. These techniques required 1 to 14 microliters unconcentrated tears. We found SDS-PAGE superior to agarose IEF to examine total tear protein pattern, and silver stain almost ten-fold more sensitive than Coomassie blue stain. Immunologic staining markedly enhanced protein detection in all tear samples and appeared to offer the definitive method to probe for a specific protein in tears. In this study prealbumin and a portion of the IgG were present in normal tears at higher than expected molecular weight, suggesting they were present in complexed form. Prealbumin and secretory component staining showed marked variability between subjects. These techniques should be applicable to examine tear proteins in a variety of ocular disease states.

Adult↗

Characterisation of two 14-3-3 genes from Trichoderma reesei: interactions with yeast secretory pathway components.

The 14-3-3 proteins are highly conserved, ubiquitously expressed proteins taking part in numerous cellular processes. Two genes encoding 14-3-3 proteins, ftt1 and ftt2, were isolated and characterised from the filamentous fungus Trichoderma reesei. FTTI showed the highest sequence identity (98% at the amino acid level) to the Trichoderma harzianum protein Th1433. FTTII is relatively distinct from FTTI, showing approximately 75% identity to other fungal 14-3-3 proteins. Despite their sequence divergence, both of the T. reesei ftt genes were equally able to complement the yeast bmh1 bmh2 double disruption. The T. reesei ftt genes were also found to be quite closely linked in the genomic DNA. A C-terminally truncated version of ftt1 (ftt1DeltaC) was first isolated as a multicopy suppressor of the growth defect of the temperature-sensitive yeast secretory mutant sec15-1. Overexpression of ftt1DeltaC also suppressed the growth defect of sec2-41, sec3-101, and sec7-1 strains. Overexpression of ftt1DeltaC in sec2-41 and sec15-1 strains could also rescue the secretion of invertase at the restrictive temperatures, and overexpression of full-length ftt1 enhanced invertase secretion by wild-type yeast cells. These findings strongly suggest that the T. reesei ftt1 has a role in protein secretion.

14-3-3 Proteins↗

Regulation of the polymeric immunoglobulin receptor by water intake and vasopressin in the rat kidney.

The polymeric immunoglobulin receptor (pIgR) transports polymeric immunoglobulins (IgA) from the basolateral to the apical surface of epithelial cells. At the apical surface, its amino-terminal domain, termed secretory component (SC), is proteolytically cleaved and released either unbound (free SC) or bound to IgA. We examined the effects of changes in water balance and vasopressin on the production and secretion of the pIgR in the rat kidney in vivo. Water deprivation induced a 2.7-fold increase in the pIgR mRNA and a 2.2-fold increase in intracellular pIgR protein compared with water-loaded animals. Physiological doses of desmopressin reproduced the effects of water deprivation on mRNA and intracellular protein levels, suggesting that pIgR expression may be regulated by a vasopressin-coupled mechanism. Secretion of free SC and secretory IgA in the urine, however, correlated directly with water intake and urine flow. These results suggest that hydration status and vasopressin may affect the mucosal immunity of the kidney by regulating at different steps the epithelial cell production and secretion of the polymeric immunoglobulin transporter/ secretory component.

Animals↗

Ontogenesis of the secretory immune system and innate defence factors in human parotid glands.

Immunoglobulin-producing cells and epithelial expression of secretory component (SC), amylase, lysozyme (Ly) and lactoferrin (Lf) were studied by immunohistochemistry to obtain information about the development of mucosal immunity. Tissue specimens were obtained from 20 fetal and 40 postnatal parotid glands. (1) Fetal specimens. Occasional IgM- and IgA- but no IgD-, IgG- or IgE- producing cells were seen (ratios, IgM:IgA:IgD:IgG:IgE approximately 4:1:0:0:0). The IgAl subclass dominated (median 90%, range 50-95%) and these cells were mostly J-chain-positive (median 97%, range 94-98%). Only few IgA2-producing cells were seen (median 10%, range 5-50%) and they were also mostly J-chain-positive (median 99%, range 98-100%). Amylase, Ly and Lf were most prominent in early fetal life, while only small amounts of SC were present. (2) Postnatal specimens. Secretory component increased markedly along with a growing number of IgA- and IgD-producing cells (IgA:IgM:IgD:IgG:IgE approximately 4:2:1:1:0). The IgAl subclass remained predominant (median 65%, range 50-90%) although the proportion of IgA2-positive cells tended to be raised (median 35%, range 10-50%). Most IgAl (median 97%, range 67-100%) and IgA2 (median 94%, range 75-100%) cells were J-chain-positive. These features probably reflected local activation of the immune system in response to environmental factors. The amount of amylase, Ly and Lf decreased shortly after delivery, perhaps because the cellular stores were emptied by postnatal increase in secretory activity.

Age Factors↗

Colloid cyst of the third ventricle. A comparative immunohistochemical study of neuraxis cysts and choroid plexus epithelium.

In an effort to shed light upon the nature of the colloid cyst, the immunohistochemical properties of 21 examples of this lesion were compared with those of other neuraxial cysts and choroid plexus epithelium. The neuraxial cysts included the following: eight Rathke's cleft cysts, 25 pituitaries containing follicular cysts of the pars intermedia, and four enterogenous cysts. Fifteen examples of normal choroid plexus and 12 choroid plexus papillomas were studied as well. These lesions were examined for localization of the following antigens: cytokeratins, epithelial membrane antigen, secretory component, carcinoembryonic antigen, prealbumin, vimentin, glial fibrillary acidic protein (GFAP), S-100 protein, neuron-specific enolase, 68-kD neurofilament protein, chromogranin, serotonin, and lysozyme, and with Leu-7 monoclonal antibodies. Five colloid cysts were immunostained with monoclonal antibodies that were specific for Clara-cell antigens and surfactant, respectively. Sugar moieties were localized using Ulex europaeus I, and Ricinus communis agglutinin I lectins. All Rathke's cleft cysts and follicular cysts of the pars intermedia as well as three selected colloid cysts were examined for pituitary hormones. The epithelial cells of colloid and enterogenous cysts, as well as those lining follicular and Rathke's cleft cyst, showed uniformly strong reactivity for cytokeratins, epithelial membrane antigen, secretory component, and vimentin, and bound Ulex europaeus lectin. Occasional cells in colloid cysts were positive for Clara cell-specific antigens. Reaction for carcinoembryonic antigen was present on the apical surface of scattered cells of colloid, follicular, and Rathke's cleft cysts. Many cells of follicles in the pars intermedia as well as individual cells of five Rathke's cleft cysts were also immunoreactive for chromogranin, S-100 protein, GFAP, and pituitary hormones. Colloid and enterogenous cysts were negative for prealbumin, S-100 protein, GFAP, and neuron-specific enolase; in all but a few instances, they failed to bind Ricinus communis agglutinin. In contrast, normal choroid plexus and choroid plexus papillomas were positive for prealbumin, S-100 protein, neuron-specific enolase, cytokeratin, vimentin, and Ricinus communis agglutinin receptors; they lacked Ulex europaeus lectin, 56/66-kD cytokeratins, and epithelial membrane antigen. Unlike normal choroid plexus, choroid plexus papillomas were often GFAP-positive. All tissues studied were nonreactive for lysosome, serotonin, and neurofilament, and with Leu-7 antibodies. This study indicates that the immunophenotype of epithelium lining colloid cysts is similar to that of other cysts showing endodermal or ectodermal differentiation and to respiratory tract mucosa. Epithelium of colloid cysts is immunohistochemically different from that of normal or neoplastic choroid plexus. These findings indicate an endodermal rather than neuroepithelial nature for colloid cysts.

Brain Diseases↗