Biomedical subjects

N Zamcheck

Publications and source records attributed to N Zamcheck.

At least 19 recordsLinked to original sources

PubMed1990

Differential reactivities of carcinoembryonic antigen (CEA) and CEA-related monoclonal and polyclonal antibodies in common epithelial malignancies.

To evaluate the role of carcinoembryonic antigen (CEA) in solving problems of tumor histogenesis in surgical pathology, monoclonal antibodies to four distinct epitopes of CEA (E-Z-EM) were applied to paraffin sections of 303 epithelial neoplasms from multiple sites. Two epitopes were CEA specific (D14 and B7.1), one was shared with nonspecific cross-reacting antigen (NCA) (B7.8), and the fourth (B18) was common to CEA, NCA, and biliary glycoprotein antigen (BGP). A sample of the tumors (n = 110) was also stained with a polyclonal anti-CEA (DAKO). Gastrointestinal adenocarcinomas, including esophageal and gastric (n = 19), small intestinal (n = 8), colorectal (n = 56), biliary tract (n = 8), and pancreatic adenocarcinomas (n = 14), were consistently positive with all five antibodies. Other predominantly gland-forming carcinomas tested, comprising lung (n = 22), ovary (n = 18), and endometrium (n = 12), were either invariably negative with all five antibodies (endometrial adenocarcinoma, non-mucinous ovarian adenocarcinoma) or demonstrated selective and variable positivity (lung: D14, 50%; ovarian mucinous: D14, 50%). Among large polygonal cell carcinomas (hepatocellular carcinoma, renal cell carcinoma, melanoma, and adrenal carcinoma), only hepatomas stained positively, showing a distinctive canalicular staining pattern with the B18 (BGP epitope) (55%) and polyclonal antibody (50%). In the small polygonal cell carcinoma category, true CEA positivity was rare in breast (D14, 10% and B7.1, 14%) and never seen in prostatic carcinomas and carcinoid tumors. A subset of these breast (8 of 42), prostate (4 of 22), and carcinoids (4 of 7) showed exclusive positivity for the B18 antibody (NCA/BGP epitope). Ovarian serous papillary carcinomas (n = 14), papillary carcinomas of thyroid (n = 12), transitional cell carcinomas of the bladder (n = 11), and mesotheliomas (n = 3) were negative with all monoclonal antibodies. Metastatic carcinomas (n = 74) showed a similar pattern of reactivity to primary tumors. The authors conclude that CEA immunostaining may assist in identifying the histogenesis of epithelial tumors in several morphologic categories; that differential reactivities of the CEA monoclonal antibody panel exceed those of the polyclonal antibody; and that the discriminating power of the monoclonal panel is related to whether (1) CEA is or is not produced or (2) NCA or BGP is produced without concomitant CEA production. There is little evidence to support a concept of site-specific CEA species.

Antibodies, Monoclonal↗

PubMed1990

Characterization of the tumorigenic and metastatic potential of a poorly differentiated human colon cancer cell line.

We characterized the tumorigenic and metastatic potential of a poorly differentiated, non-CEA-producing colon cancer cell line, MIP-101, after injection at different sites in athymic mice. After subcutaneous and intrasplenic injection tumor grew locally in 100 and 50%, respectively, but no metastases were found, even after intravenous injection. Intraperitoneal implantation, however, resulted in a high tumor take (10/10) and subsequent liver colonization (8/10 mice). Exogenous CEA prior to intrasplenic injection induced metastasis in 7/8 mice (in 2 mice to the liver and in 5 mice to the lung). Intrasplenic injection of CX-1, a good CEA producer, resulted in hepatic metastases in 100% of the animals. These data suggest a direct or indirect role of CEA in the metastatic process. We conclude that MIP-101 has a high tumorigenic and invasive potential but a low metastatic proclivity, except when grown in the peritoneum, and that pretreatment of tumor-bearing animals with CEA affects the metastatic proclivity.

Adenocarcinoma↗

PubMed1989

Receptor-mediated endocytosis of carcinoembryonic antigen by rat alveolar macrophages in vitro.

Uptake of carcinoembryonic antigen (CEA) by isolated rat alveolar cells was time, temperature, and concentration dependent (Kuptake = 2.4 x 10(-7) M). Pretreatment of the alveolar cells with colchicine inhibited internalization of CEA. Uptake of 125I-labeled CEA by alveolar cells required divalent cations and was inhibited by cold CEA and nonspecific cross-reacting antigen (NCA). The carbohydrate portion of CEA was modified by neuraminidase treatment and Smith degradation. The modified glycoproteins inhibited endocytosis by the alveolar macrophages, thus excluding nonreducing terminal carbohydrate residues as the recognition site of the receptor. Endocytosis of CEA was independent of native protein conformation since performic acid oxidized CEA and glycopeptides produced by pepsin digestion were inhibitory. Rat alveolar macrophages bound CEA with similar specificity to that of rat Kupffer cells. Alveolar macrophages, unlike Kupffer cells, did not rapidly exocytose the internalized CEA. Neither P388D1, a macrophage-like murine cell line, nor murine peritoneal exudate cells were capable of endocytosing CEA in vitro.

Animals↗

PubMed1988

A cell surface glycoprotein expressed by colorectal carcinomas including poorly differentiated, noncarcinoembryonic antigen-producing colorectal tumors.

A monoclonal antibody to a cell surface glycoprotein on human colorectal carcinomas was raised using the undifferentiated colon carcinoma cell line MIP 101 as the immunogen. This antibody, ND4, is an IgG2a which does not cross-react with carcinoembryonic antigen (CEA), non-specific cross-reacting antigen, or blood group substances A, B, and H. Immunoprecipitation using lysates of cells grown in [35S]methionine or [3H]glucosamine and lysates of cells surface labeled with 125I showed binding to a cell surface glycoprotein with a molecular weight of approximately 160,000. Indirect immunofluorescence showed binding to the cell surface of 14 of 15 human colorectal carcinoma cell lines including six of six that do not secrete CEA. Two of seven human noncolorectal carcinoma lines and one of six nonhuman cell lines also bound antibody. Immunoperoxidase staining of formalin-fixed tissues showed prominent antibody binding with 19 of 33 (58%) human colorectal carcinomas, including five of six poorly differentiated tumors, five of 43 (12%) normal colonic mucosal biopsies, and one of 17 (6%) normal noncolonic tissues. One of 11 (9%) noncolonic tumors, a gastric adenocarcinoma, stained with ND4. Preliminary data obtained by a nonquantitative nitrocellulose dot-immunoassay have tentatively identified this glycoprotein in the serum of 15 of 37 (41%) patients with colorectal cancer. Three of the 15 patients had early stage disease and normal CEA levels (less than 2.5 ng/ml). Three patients had circulating antigen detectable preoperatively but not after tumor resection. Only one of 11 (9%) sera samples from normal subjects was positive. The characteristics of ND4 suggest that it may be of value in monitoring patients with colorectal carcinomas who do not have plasma CEA elevations. It may also be of value in the differential diagnosis of metastatic, poorly differentiated adenocarcinomas of unknown primary origin.

Animals↗

PubMed1988

Serum beta-N-acetyl hexosaminidase and bile acid levels in patients with benign and malignant biliary obstruction.

beta-N-Acetyl hexosaminidase (beta-NAH), a lysosomal enzyme, was measured in the plasma of 15 patients with malignant extrahepatic biliary obstruction, 14 with benign extrahepatic obstruction, and 15 with long-standing benign intrahepatic cholestasis. beta-NAH was correlated with total serum bile acid levels. The correlation was significant (P less than 0.05) for the malignant and benign intrahepatic obstructions but not for the benign extrahepatic obstructions. This is consistent with the idea that circulating high levels of bile acids in patients with long-standing biliary obstruction may cause damage to Kupffer cell membranes and to their receptors for beta-N-acetyl hexosaminidase, impeding the clearance of the enzyme from the circulation resulting in elevated serum levels.

Adenoma, Bile Duct↗

PubMed1988

Hepatic clearance and metabolism in the rat of a human breast cancer associated glycoprotein (GCDFP-15).

Gross Cystic Disease Fluid Protein (GCDFP-15) is a 60,000 dalton glycoprotein isolated from human breast cyst fluid, composed of four 15,000 dalton monomers. Carbohydrate analysis indicates that each monomer has a single carbohydrate chain of the complex type. GCDFP-15 intravenously injected into rats showed a rapid circulatory clearance, the rate of clearance being faster in female animals [t1/2 = 12.8 (+/- 2.0) min. females, and 16.7 (+/- 2.6) min. males]. The major organs of clearance were the liver (70%) and kidneys (15%). Immunoperoxidase staining showed localization in Kupffer cells and the proximal convoluted tubules of the kidney. Removal of sialic acid from GCDFP-15 resulted in a more rapid clearance (t1/2 = 2.2 min) by the liver (85%). This clearance was inhibited by coinjection of asialo alpha 1 acid glycoprotein. About 3% of GCDFP-15 was excreted in bile with a transit time through the liver of 38 min. Examination of the uptake of GCDFP-15 by isolated rat Kupffer cells showed that yeast mannan, fucosylated BSA, and carcinoembryonic antigen (CEA) failed to inhibit uptake, though the binding of GCDFP-15 was clearly saturable. This suggests that a novel receptor system on the rat Kupffer cell may be responsible for GCDFP-15 clearance.

Animals↗

PubMed1988

The effect of sodium butyrate and retinoic acid on growth and CEA production in a series of human colorectal tumor cell lines representing different states of differentiation.

The effect of sodium butyrate and retinoic acid added singly or in combination on substrate-dependent growth, colonization efficiency in soft agar, and carcino-embryonic antigen (CEA) production in three human colorectal carcinoma cell lines differing in their degree of differentiation was studied. All three colon cancer cell lines regardless of their state of differentiation had their growth markedly slowed by sodium butyrate, and to a lesser extent by retinoic acid. When both agents were added together, a small synergistic inhibition of growth was noted in all the cell lines. Butyrate eliminated colony formation in soft agar in all three cell lines, however, retinoic acid only reduced colony formation in the well differentiated cell line DLD-2. Sodium butyrate was able to induce CEA production in the undifferentiated cell (MIP-101) and the moderately differentiated cells (clone D) which were previously negative for this marker. It also enhanced the baseline production of CEA in the well differentiated cells (DLD-2). Retinoic acid did not induce CEA production in clone D or MIP-101 cells, but did enhance the production of CEA in DLD-2 cells. When both retinoic acid and sodium butyrate were added together, CEA production was either additive (DLD-2) or was inhibited (clone D and MIP-101). One explanation of these results is that only well differentiated cells have functional cellular retinoic acid-binding protein (cRABP), and that certain actions of retinoic acid (inhibition of anchorage-dependent growth) are independent of the presence of cRABP.

Butyrates↗

PubMed1988

Search for useful biomarkers of pre- or early malignant colonic tumors.

1. CEA, a well established marker for benign and malignant colonic tumors is widely used for tissue staining and body fluid measurement. Highly specific monoclonal antibodies are now available. It is likely that CEA gene(s) will be available soon. 2. Monoclonal antibodies to blood group precursor antigens, especially extended LeX and LeY are also available and are known to detect premalignant lesions. 3. The demonstration that LeY is expressed in purified CEA specimens suggests a complementary relationship between the two markers of possible clinical utility. 4. Systematic comparison of both families of marker is timely. 5. Experienced pathologists have classified and standardized the histology of adenomatous polyps and their premalignant counterparts. The use of serial sections of identical tissues will permit comparison of several candidate markers in the same lesion. Selection of lesions which contain benign, malignant, and invasive components in the same section will provide best control, minimizing the need for exhaustive studies. 6. Laminin staining gives useful indication of early invasion through the basement membrane. It will complement morphologic and marker evidence for early malignancy and invasion. 7. It is unnecessary to investigate all polyps. Focus should be on high risk patients with (1) large polyps, severe dysplasia and advanced villous change, (2) synchronous polyps and invasive cancer, and (3) familial and other multiple polyposis disorders. 8. A plethora of other candidate markers is available, only a few of which are mentioned.

Antibodies, Monoclonal↗

PubMed1987

Evaluation of chimpanzee antiserum to human carcinoembryonic antigen.

An adult chimpanzee (Pan troglodyte) with an endogenous circulating carcinoembryonic antigen (CEA) level of 60 ng/ml was immunized s.c. with human CEA. After 1 year of immunizations, the anti-human CEA antibody titer had plateaued. This chimpanzee antiserum demonstrated high avidity specific recognition of human CEA and showed ionic strength effects for CEA recognition similar to those previously described for goat and baboon anti-CEA antisera. Radioimmunoassay of 93 human plasma samples for CEA content using chimpanzee anti-CEA versus Roche goat anti-CEA antisera gave essentially identical results (R = 0.985). Endogenous CEA in chimpanzee blood was very poorly identified by chimpanzee anti-human CEA antisera compared to Roche goat antisera. Column chromatography of human and chimpanzee CEA in the presence of chimpanzee anti-CEA antibody showed only reactivity for the human CEA. In addition, chimpanzee antiserum had only minimal blocking effect on the binding of either goat or baboon antiserum to human CEA. We conclude from these studies that chimpanzee anti-human CEA antiserum recognized a determinant(s) on human CEA which was different from these recognized by goat or baboon antiserum to human CEA and this determinant(s) was poorly represented on chimpanzee CEA. In contrast, the human CEA determinant(s) recognized by baboon and goat anti-CEA antiserums were readily detected on chimpanzee (CEA).

Animals↗

PubMed1987

Isolation and characterization of an undifferentiated human colon carcinoma cell line (MIP-101).

An undifferentiated human colon carcinoma cell line was established from tumor tissue obtained from metastasis to the liver of colonic adenocarcinoma in a patient with fulminant Dukes D colorectal carcinoma. Histological analysis of the tumor biopsy from the liver confirmed the hospital pathology report of poorly differentiated colonic adenocarcinoma. Explants of this tumor tissue xenografted into a nude mouse were used to establish an epithelioid-like cell culture line, MIP-101. The cell line formed tumors in nude mice that histologically appeared undifferentiated and did not stain for carcinoembryonic antigen (CEA). No CEA was present either by radioimmunoassay (RIA) of the culture supernatant or by immunoperoxidase staining of the tumors or monolayers. MIP-101 appears to be one of the most undifferentiated human colon carcinoma cells lines available. It should prove useful in the search for markers of undifferentiated colonic cancer and in studies of colonic cancer differentiation.

Adenocarcinoma↗

PubMed1986

Fluoxymesterone stimulation of tumor marker secretion in patients with breast carcinoma.

The gross cystic disease fluid protein of 15,000 MW (GCDFP-15) has been demonstrated to be a circulating glycoprotein tumor marker for breast carcinoma in approximately 40% of patients with advanced disease. A recent retrospective analysis of plasma GCDFP-15 levels in patients with advanced breast cancer suggested that androgen therapy could cause significant increases in plasma levels in the absence of disease progression. In order to evaluate the frequency, time course, and intensity of the androgen effect on GCDFP-15 production, a prospective study was initiated. Twenty-nine patients with stage IV breast carcinoma were treated with fluoxymesterone (20 or 30 mg/d). Plasma levels of GCDFP-15 and carcinoembryonic antigen (CEA) were measured by radioimmunoassay before and at various times during therapy. By day 6 of therapy, plasma GCDFP-15 had increased significantly (p = 0.03) from a mean basal level of 58 +/- 12 ng/ml to 160 +/- 60 ng/ml. By contrast, the mean CEA levels in the same patients increased only from 36 +/- 14 ng/ml. The distribution of percent increases in plasma GCDFP-15 was not uniform, but patients with high (greater than 82 ng/ml) basal levels had marked (greater than or equal to 75%) increases in 6/6 (100%) cases, whereas patients with low (less than 30 ng/ml) basal levels had similar increases in only 2/15 (13%) cases. Urinary excretion of GCDFP-15 usually paralleled the increases in plasma levels of the glycoprotein during the first six days of therapy. A linear correlation between percent change in plasma and percent change in urinary GCDFP-15 was demonstrated. A permanent cell line of human breast carcinoma, T47-D, was stimulated to secrete GCDFP-15 in vitro by androgen, but not by estrogen. From these data, we conclude that androgens can specifically stimulate secretion of GCDFP-15 by breast carcinoma tissue in most patients with elevated plasma levels of GCDFP-15, and in some patients with normal levels. The stimulation occurs within days and is not associated with clinical signs of tumor growth.

Apolipoproteins↗

PubMed1986

Capture and detection of carcinoembryonic antigen on antibody coated beads used in enzyme immunoassay.

We have evaluated antibody coated beads for capture and detection of carcinoembryonic antigen (CEA). Assay parameters of time, temperature, buffer molarity, specificity of antibody on the bead and reagent addition sequence have been studied. Optimal assay kinetics occurred at a temperature of 45 degrees C and a buffer molarity of 0.1M or above. The type and quantity of antibody on the bead surface were also critical to optimal CEA detection. Beads coated with baboon or goat anti-CEA antibody were able to capture a higher percentage of CEA than monoclonal mouse anti-CEA antibody or guinea pig anti-CEA antibody. The sequence of addition of CEA, anti-CEA antibody coated bead, and anti-CEA-horse radish peroxidase conjugate was important for optimal CEA detection. Formation of an immune complex of CEA with the anti-CEA horse radish peroxidase conjugate prior to capture of the CEA on an antibody bead resulted in the optimal detection of CEA.

Animals↗

PubMed1986

Serial levels of CA 19-9 and CEA in colonic cancer.

The use of serial carbohydrate antigen (CA) 19-9 assays was assessed by comparison with serial carcino-embryonic antigen (CEA) levels on the plasmas of 53 patients with colorectal carcinoma. The patients had all undergone resection for their primary tumors and in six instances subsequent resections for hepatic metastases. Initial CA 19-9 levels were greater than or equal to 37 U/mL in 22 of the 53 patients (41%) and in 68% of the patients with metastatic disease. Similar trends of serial CA 19-9 and CEA levels were found in 79% of the 53 patients. One patient with initially normal CEA levels had elevated CA 19-9 levels from the start. In ten of the 53 patients (19%), serial CA 19-9 levels remained low despite tumor recurrence or progression, and despite increasing CEA levels above 5 ng/mL. The increasing serial CEA trends predicted recurrence in 88% and increasing CA 19-9 trends in 50% of cases, which was increased to 70% by including trends of CA 19-9 levels below 37 U/mL. Following hepatic lobectomy, both serial CEA and CA 19-9 levels decreased rapidly. Used alone, serial CA 19-9 levels did not appear to be as sensitive as standard CEA in this retrospective study of selected patients.

Adult↗

PubMed1985

Ultrastructural evidence of dimethylformamide-induced differentiation of cultured human colon carcinoma cells. Increased expression of desmosomes.

N,N-dimethylformamide (DMF) induces differentiation of human colon carcinoma (DLD-1) cells in culture and reduces their tumorigenicity in nude mice. The current investigation analyzed DLD-1 (clone D) cells for ultrastructural evidence of differentiation. Examination of treated and untreated confluent monolayers by transmission electron microscopy revealed an occasional intracytoplasmic lumen indicative of adenocarcinoma. DMF-treated cells showed no signs of a toxic reaction. Cytoplasmic organelles were essentially unchanged except for an increase in tonofilaments and associated desmosomes. The number of desmosomes per unit length of contiguous cell border increased almost sixfold in treated monolayers. No other type of cell junction was seen. The increased frequency of desmosomes in DMF-treated cultures is significant because of the direct correlation known to exist between the number of desmosomes and degree of differentiation of some human carcinomas. Desmosomes serve as foci of cell adhesion and are reduced in number in some invasive tumors. Whether the supernumerary desmosomes in DMF-treated cells contribute to the reduction in malignant behavior of these cells in vivo remains to be determined.

Acetylation↗

PubMed1985

Early gastric cancer. Clinicopathologic study.

The incidence and clinicopathologic features of early gastric cancer encountered among surgical specimens from gastric resections for carcinoma in a recent three-year period, 1977 to 1979, at the Mallory Institute of Pathology were studied and compared with those of a pre-endoscopic period 10 years earlier, 1967 to 1969. It was found that early gastric cancer now comprises a greatly increased proportion of lesions leading to gastric resection, mainly as a result of endoscopy and biopsy of gastric ulcers of benign appearance. In the recent period, there were six early gastric cancers in a total of 22 gastric resection specimens compared with one in 27 gastric resections performed for carcinoma in the pre-endoscopy period. Five of the six patients in the recent period are alive without evidence of disease four to five years following surgical resection. The single patient in the earlier period died postoperatively. Applying the classification of the Japanese Endoscopic Society, there were three depressed or ulcerated lesions (type IIc or III), three elevated or polypoid lesions (type I or IIa), and a single flat lesion (type IIb). All three ulcerated lesions were interpreted as benign peptic ulcers on conventional upper gastrointestinal studies. Findings on endoscopic biopsy were positive in all cases (six of six). Although not encountered frequently in the United States, early gastric cancer, nonetheless, appears to be indistinguishable from the disease as it is described in Japan in terms of its pathologic morphology, growth patterns, coexistent or related lesions of the stomach, and curability by surgical resection. If early gastric cancer is to be recognized more frequently, knowledge of the disease and a high index of suspicion on the part of physicians are essential.

Adenocarcinoma↗

PubMed1985

Serum beta-N-acetyl hexosaminidase (beta-NAH) as a discriminant between malignant and benign extrahepatic biliary obstruction: comparison with carcinoembryonic antigen (CEA).

Fifty-one patients (16 with malignant extrahepatic biliary obstruction, ten with benign extrahepatic biliary obstruction, eight with alcoholic liver disease, five with viral hepatitis and 12 with liver metastases) and 19 adult healthy controls were studied with determinations of beta-N-acetyl hexosaminidase (a lysosomal enzyme which is cleared from the circulation by the Kupffer cells), carcinoembryonic antigen (CEA), serum bilirubin, alkaline-phosphatase and aspartate aminotransferase (AST). Both CEA and beta-NAH were elevated in each disease group. Elevated beta-NAH levels distinguished between benign and malignant extrahepatic biliary obstruction better than CEA levels. Beta-NAH levels for the malignant and the benign groups were 47.6 +/- 14.7 U/l and 23.0 +/- 4.7 U/l (mean +/- S.D.) respectively. The groups differed significantly (P less than 0.001). Plasma CEA levels for both groups were 18.7 +/- 38.9 and 7.2 +/- 3.3 ng/ml (mean +/- S.D.) respectively. Beta-NAH levels for the 19 normal controls were 15.8 +/- 3.5 U/l (mean +/- S.D.). Beta-NAH also was significantly elevated in patients with hepatic metastases (36.9 +/- 20.1 U/l). In 25 cancer patients with metastases other than in the liver beta-NAH levels (18.3 +/- 5.2) were not significantly elevated over the control group. It has potential value as a marker for non-CEA-producing liver metastases.

Alkaline Phosphatase↗

PubMed1985

Differences in CEA values determined by EIA and RIA in patients with benign and malignant biliary obstructions.

Serial carcinoembryonic antigen (CEA) levels were determined by both the Roche RIA and Abbott EIA methods in 11 patients with pancreatic cancer (9 with extrahepatic biliary obstruction); 7 with benign extrahepatic obstruction; 26 with colonic cancer without biliary obstruction; and 12 normal, non-smoking controls. The Roche/Abbott CEA ratios in the patients with malignant and benign obstruction (mean ratios = 3.05 and 3.08, respectively), were significantly higher than those in patients with colon cancer without biliary obstruction and in normal controls (mean ratios = 1.35 and 1.06, respectively). Four patients with malignant obstructions were decompressed successfully (bilirubin less than or equal to 1.5 mg/dL); the ratios for two of these patients declined to "normal" (1.0), while the ratios for the other two remained elevated despite decompression. These findings show that some patients with benign or malignant biliary obstruction have elevated CEA levels when measured by the Roche RIA but not with the Abbott EIA.

Adult↗

PubMed1985

Receptor-mediated endocytosis of carcinoembryonic antigen by rat liver Kupffer cells.

In vivo, carcinoembryonic antigen (CEA) is removed from the circulation by the liver Kupffer cells. Immunologically identifiable CEA is transferred from these macrophages to the hepatocytes, where degradation is completed. Circulatory clearance of CEA is specific, rapid [t1/2 = 3.7 +/- 0.9 (S.D.) min], and saturable. In vitro, Kupffer cells take up CEA by a saturable process which is time/temperature dependent and colchicine sensitive. Isolated Kupffer cells endocytose CEA with an apparent Km of 6 X 10(-8) M. There are approximately 16,000 CEA binding sites per cell. Nonspecific cross-reacting antigen (NCA), a glycoprotein structurally similar to CEA, is recognized with lower affinity by the same receptor. Endocytosis is independent of the nonreducing terminal sugars on the molecule: CEA modified by Smith degradation inhibits Kupffer cell recognition of native CEA. Since performic acid oxidized CEA also inhibits endocytosis, receptor binding is similarly independent of intact protein conformation. Isolated Kupffer cells have mannose and/or N-acetyl glucosamine receptor activity but do not internalize CEA by that mechanism. Galactose-terminated glycoproteins impede CEA and NCA clearance in vivo but not Kupffer cell endocytosis in vitro. Radiolabeled CEA released from isolated Kupffer cells following endocytosis shows no apparent molecular weight change. However, the released CEA contains species with higher isoelectric points, suggesting that perhaps the removal of sialic acid and the resulting exposure of galactose residues mediate the subsequent transfer to the hepatocyte.

Animals↗