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C H Zhang

Publications and source records attributed to C H Zhang.

At least 19 recordsLinked to original sources
PubMed1998

The equine homologue of LFA-1 (CD11a/CD18): cellular distribution and differential determinants.

The equine homologue of the leucocyte integrin LFA-1 (CD11a/CD18) has been characterized using a panel of four monoclonal antibodies (mAbs). The antibodies labelled almost all leukocytes, thymocytes and lymph node cells from normal horses, and immunoprecipitated two noncovalently associated polypeptides with molecular weights of 180 kDa and 100 kDa, respectively. The antigen recognized by one mAb could be precipitated by another in this cluster in a sequential immunoprecipitation assay. The mAbs, however, did not block the activities on lymphocyte function of one another. A mAb to the beta subunit of human LFA-1 cross-reacted with equine LFA-1, but an antibody to its alpha subunit did not, suggesting that the beta subunit of the leukocyte integrin may be more highly-conserved. Functionally, H20A and a human CD18 antibody (MHM23) inhibited phorbol ester-mediated homotypic lymphocyte aggregation, whereas mAb CZ3.2 induced rather than inhibited the homotypic cell aggregation. The formation of lymphocyte aggregates induced by CZ3.2 was not blocked by the inhibitory antibodies H20A or MHM23. CZ3.1 seemed to have little inducible or inhibitory effects on homotypic cell aggregation. The mAb CZ3.1 defined a unique LFA-1 determinant present on granulocytes, but absent on lymphocytes in members of an extended horse family, in contrast to the other antibodies which labelled both granulocytes and lymphocytes from these animals. In all other horses tested, no differences in reactivity of CZ3.1 and the other LFA-1 antibodies were observed when the antibodies were tested on lymphocytes or granulocytes. Our results indicate that common epitopes are shared' between human and equine LFA-1, and that the described panel of monoclonal antibodies identifies distinct determinants present on the equine LFA-1 molecule. The following monoclonal antibodies used in this study were given official workshop designations at the Second International Workshop on Equine Leukocyte Antigens (Lunn et al., 1998) CZ3.1 (Cor) = W45; CZ3.2 (Cor) = W77.

Animals↗
PubMed1998

Mechanism of the dynorphin-induced dualistic effect on free intracellular Ca2+ concentration in cultured rat spinal neurons.

In order to study the different mechanisms of dynorphin spinal analgesia and neurotoxicity at low and high doses, the effects of various concentrations of dynorphin A-(1-17) on the free intracellular Ca2+ concentration ([Ca2+]i) in the cultured rat spinal neurons were studied using single cell microspectrofluorimetry. While dynorphin A-(1-17) 0.1-100 microM had no significant effect on basal [Ca2+]i, dynorphin A-(1-17) 0.1 and 1 microM significantly decreased the high KCl-evoked peak [Ca2+]i by 94% and 83% respectively. Dynorphin A-(1-17) 10 and 100 microM did not affect the peak [Ca2+]i following K+ depolarization, but in all these neurons there was a sustained and irreversible rise in [Ca2+]i following high-K+ challenge. Pretreatment with the specific kappa-opioid receptor antagonist nor-binaltorphimine 10 microM, but not the competitive NMDA receptor antagonist, DL-2-amino-5-phosphonovalerate (APV) 10 microM, significantly blocked the inhibitory effect of dynorphin A-(1-17) 0.1 microM on peak [Ca2+]i. However, APV 10 microM and nor-binaltorphimine 10 microM significantly antagonized the sustained rise in [Ca2+]i induced by a high concentration of dynorphin A-(1-17) 10 microM. Furthermore, in the presence, and following the addition, of increasing concentrations of dynorphin A-(1-17) (0.1, 1, 10 and 100 microM), the high concentrations of dynorphin A-(1-17) failed to produce a sustained rise in peak [Ca2+]i. These results suggested that dynorphin exerted a dualistic modulatory effect on [Ca2+]i in cultured rat spinal neurons, inducing a sustained and irreversible intracellular Ca2+ overload via activation of both NMDA and kappa-opioid receptors at higher concentrations, but inhibiting depolarization-evoked Ca2+ influx via kappa-opioid but not NMDA receptors at lower concentrations. Serial addition of graded concentrations of dynorphin A-(1-17) prevented the effect of high concentrations of dynorphin A-(1-17) on [Ca2+]i.

Animals↗
PubMed1997

Factors influencing hematologic toxicity of radioimmunotherapy with 131I-labeled anti-carcinoembryonic antigen antibodies.

BACKGROUND: Several investigators have reported a considerable variability in the observed hematologic toxicity after radioimmunotherapy (RAIT) with monoclonal antibodies (MoAb) given at similar amounts of radioactivity based on body surface area and/or similar radiation absorbed doses given to the red marrow. The authors investigated various factors potentially affecting hematologic toxicity after RAIT with 131I-labeled anti-carcinoembryonic antigen (CEA) MoAb to identify the statistically significant factors from those commonly perceived clinically to substantially contribute to this toxicity. METHODS: Ninety-nine patients who received 131I-labeled anti-CEA MoAb for the treatment of CEA-producing cancers were assessed for platelet and white blood cell toxicity based on the common Radiation Therapy Oncology Group criteria. Multivariate regression analysis was used to identify the statistically significant factors affecting toxicity among the following variables: red marrow dose, baseline platelet and white blood cell counts, bone and/or marrow metastases, prior chemotherapy or radiotherapy, timing of prior chemotherapy or radiotherapy in relationship to RAIT, type and number of prior chemotherapeutic regimens, age, sex, antibody form, and cancer type. RESULTS AND CONCLUSIONS: Red marrow dose, baseline platelet or white blood cell counts, multiple bone and/or marrow metastases, and chemotherapy 3-6 months before RAIT were the only four significant factors affecting hematologic toxicity according to multivariate analysis. The identification of bone and/or marrow metastases and recent chemotherapy as significant factors for hematologic toxicity could be important in the design of future clinical trials.

Adolescent↗
PubMed1997

Differential regulation of neurogenesis by the two Xenopus GATA-1 genes.

Previously, we have shown that the ventralizing factor bone morphogenetic protein 4 (BMP-4) can inhibit Xenopus neurogenesis. The erythroid transcription factor GATA-1 functions downstream of the BMP-4 signaling pathway and mediates BMP-4-induced erythropoiesis. We have found that similar to BMP-4, GATA-1b inhibits neuralization of Xenopus animal cap (AC) cells. The neural inhibition is not seen with GATA-1a, although both GATA-1a and GATA-1b RNAs are translated at the same efficiency and induce globin expression equally in AC cells. GATA-1b RNA injection into AC cells neither induces expression of Xbra (a general mesoderm marker) nor affects expression of XK81 (epidermal keratin) or BMP-4 and Xvent-1 (two ventral markers). These data suggest that GATA-1b retains the epidermal fate of the AC. Intact GATA-1b protein is required for both inhibition of neurogenesis and induction of globin expression. Our findings indicate that GATA-1b can function in ectoderm to specifically regulate neural inducing mechanisms, apparently related to the expression of chordin, a neuralizing gene. Furthermore, tadpole stage embryos injected with GATA-1b are devoid of all dorsoanterior structures including neural tissue. This report provides evidence that the two transcription factors, derived from a recent genome duplication, share a common biological activity (stimulation of erythropoiesis) while also exhibiting a distinct function (inhibition of neurogenesis).

Animals↗
PubMed1997

Cloning, characterization, and heterologous expression of exon-4-containing amelogenin mRNAs.

The formation of dental enamel is dependent upon amelogenins, a family of proteins constituting most of the developing enamel matrix. Depending upon the species, these enamel proteins are expressed from either one or two copies of the amelogenin gene. Each gene directs the synthesis of a variety of amelogenin isoforms through alternative splicing of their pre-mRNA transcript(s). Before the role of amelogenins in dental enamel formation can be better understood, one must know the isoforms that are secreted and their biochemical properties. Previously, we cloned and characterized 7 mouse amelogenin RNA messages generated by alternative splicing. The largest amelogenin cDNA encoded a 194-residue amelogenin isoform which was the only clone to contain the 42-nucleotide exon 4 segment. Anti-peptide antibodies raised against the derived translation of this exon revealed an unexpectedly diverse assortment of murine amelogenins, suggesting that additional splicing variants could contain the exon 4 coding region. Using exon-4-specific oligonucleotide primers, we have amplified, cloned, and characterized three different amelogenin RNA messages. These messages encode amelogenin polypeptides (exclusive of signal peptides) 194, 170, and 73 amino acids in length. The isotope-averaged molecular weights for the deduced, single-phosphorylated, proteins are 21,897.1, 19,113.9, and 8176.5 Daltons, respectively. Splice-site selection for the generation of these mRNAs was identical to that of the previously characterized messages for the M180, M156, and M59 except for the inclusion of exon 4. The exon-4-containing amelogenin isoforms were heterologously expressed in E. coli by means of the pET11 expression system (Novagen, Madison, WI).

Amelogenin↗
PubMed1997

Sheathlin: cloning, cDNA/polypeptide sequences, and immunolocalization of porcine enamel sheath proteins.

Sheath proteins designate low-molecular-weight non-amelogenin enamel polypeptides and their parent protein, which concentrate in the sheath space separating rod and inter-rod enamel (Uchida et al., 1995). Two porcine sheath proteins, with apparent molecular weights of 13 and 15 kDa, are characterized by protein sequencing. The primary structures of these polypeptides match a portion of the derived amino acid sequences of clones isolated from a porcine enamel organ epithelia-specific cDNA library. Sheath protein RNA messages differ by the inclusion or deletion of a 45-nucleotide segment and by the use of three alternative polyadenylation/cleavage sites. The secreted proteins are 395 and 380 residues in length, with molecular masses of 42,358 and 40,279 Daltons and calculated isoelectric points of 6.3 and 6.7, respectively. Polyclonal antibodies were raised against a synthetic peptide having the sheathlin-specific sequence EHETQQYEYSGGC. Immunohistochemistry with this antibody demonstrates that the protein encoded by the sheathlin cDNA is preferentially localized in the sheath space. We propose that the porcine sheath proteins and their proteolytic cleavage products be designated "sheathlin".

Amino Acid Sequence↗
PubMed1997

Cloning and characterization of porcine enamelin mRNAs.

Dental enamel forms by matrix-mediated biomineralization. The components of the developing enamel matrix are generally specific for that matrix. The primary structures of three enamel proteins-amelogenin, tuftelin, and sheathlin (ameloblastin/amelin)-have been derived from cDNA sequences. Here we report the cloning and characterization of mRNA encoding a fourth enamel protein: enamelin. The longest porcine enamelin cDNA clone has 3907 nucleotides, exclusive of the poly(A) tail. The primary structure of the secreted protein is 1104 amino acids in length. Without post-translational modifications, the secreted protein has an isotope-averaged molecular mass of 124.3 kDa and an isoelectric point of 6.5. Polymerase chain-reaction phenotyping of enamelin cDNA suggests that porcine enamelin transcripts are not alternatively spliced and use a single polyadenylation/cleavage site. Immunohistochemical and Western blot analyses with an affinity-purified antipeptide antibody specific for the enamelin carboxyl terminus demonstrate that enamelin is synthesized and secreted by secretory-phase ameloblasts. The parent protein is a 186-kDa glycoprotein that concentrates along the secretory face of the ameloblast Tomes' process. Intact enamelin and proteolytic cleavage products containing its carboxyl terminus are limited to the most superficial layer of the developing enamel matrix, while other enamelin cleavage products are observed in deeper enamel.

Amino Acid Sequence↗
PubMed1997

Variables influencing tumor dosimetry in radioimmunotherapy of CEA-expressing cancers with anti-CEA and antimucin monoclonal antibodies.

UNLABELLED: In this study, we examined the factors that may influence tumor dosimetry in the radioimmunotherapy of solid, CEA-expressing cancers. METHODS: Data from 119 tumors in 93 patients with CEA-expressing cancers were analyzed. The patients underwent radioimmunotherapy with the 131I-labeled IgG1 anti-CEA antibodies NP-4 (Ka = 10(8) M-1) or MN-14 (Ka = 10(9) M-1), its humanized form hMN-14, as well as the anticolon-specific antigen-p (CSAp) antibody, Mu-9. For dosimetry, the biodistribution, targeting kinetics and cumulated activity of tumors and organs were determined from planar and SPECT imaging. RESULTS: An inverse logarithmic relationship between tumor size and antibody uptake was found for both anti-CEA antibodies, whereas no such relationship was found for Mu-9. The absolute tumor uptake was identified as the most important factor determining the radiation dose to the tumor (r = 0.9), with the biological half-life of the antibody in the tumor being of secondary importance (r = 0.5). No significant difference in tumor uptake was found between both anti-CEA antibodies, despite their tenfold difference in affinity. At comparable masses, colorectal and medullary thyroid cancers had significantly higher tumor uptakes (p = 0.02), as well as tumor-to-red marrow dose ratios, than other cancer types. The tumor half-lives of the anti-CEA antibodies were significantly lower in colorectal than in all other tumor types (p = 0.01). CONCLUSION: In radioimmunotherapy, tumor uptake appears to be the most important dose-determining factor. Differences in antibody affinity are reflected by differences in the biological half-life, not the absolute uptake. Especially favorable conditions for anti-CEA antibodies seem to prevail in colorectal cancer patients having minimal disease, as well as in medullary thyroid cancer, where cytotoxic tumor doses might be expected. Antimucin antibodies may have a particular advantage in the treatment of patients with larger colorectal tumors.

Adenocarcinoma↗
PubMed1997

Phase I/II clinical radioimmunotherapy with an iodine-131-labeled anti-carcinoembryonic antigen murine monoclonal antibody IgG.

UNLABELLED: The aim of this study was to determine, in a Phase I/II clinical trial, the pharmacokinetics, dosimetry and toxicity, as well as antitumor activity, of the 131I-labeled murine anti-carcinoembryonic antigen (CEA) monoclonal antibody, NP-4 (IgG1 subtype). METHODS: A total of 57 patients with CEA-expressing tumors (29 colorectal, 9 lung, 7 pancreas, 6 breast and 4 medullary thyroid cancer patients), mostly in very advanced stages, were treated. The patients underwent a diagnostic study (1-3 mg of IgG and 8-30 mCi of 131I) to assess tumor targeting and to estimate dosimetry, followed by the therapeutic dose (4-23 mg and 44-268 mCi), based on the radiation dose to the red marrow. Imaging was performed from 4-240 hr postinjection (planar and SPECT). Blood and whole-body clearance were determined; radiation doses were calculated by the Medical Internal Radiation Dose scheme. RESULTS: Red marrow doses ranged from 45 to 706 cGy, and whole-body doses ranged from 31 to 344 cGy. Differences in pharmacokinetics were found between different types of CEA-producing tumors: blood T 1/2 was significantly lower in colorectal cancer when compared to all other tumor types (21.4 +/- 11.1 hr versus 35.8 +/- 13.2 hr, p < 0.01), as was also whole-body t 1/2. Myelotoxicity was dose-limiting, and its severity was related to the types of prior therapy and extent of bone marrow involvement. In patients without prior radiation or chemotherapy, marrow doses as high as 600 cGy were tolerated without evidence of dose-limiting toxicity. No major toxicity to other organs was observed. Tumor doses were inversely related to the tumor mass and ranged between 2 and 218 cGy/mCi. Modest antitumor effects were seen in 12 of 35 assessable patients (1 partial remission, 4 minor/mixed responses and 7 with stabilization of previously rapidly progressing disease). CONCLUSION: These results suggest that prior chemotherapy or external beam radiation is an important risk factor for the development of hematological toxicity in radioimmunotherapy and that higher radiation doses may be delivered to tumors of patients without prior therapy compromising the bone marrow reserve. The different and, in the individual cases, unpredictable clearance rates suggest the necessity of dosimetry-based treatment planning rather than mCi/m2 dosing. Small tumors seem to be more suitable for radioimmunotherapy because of their favorable dosimetry, but to achieve better therapeutic results in patients with bulky disease, the application of higher, potentially myeloablative doses is indicated.

Aged↗
PubMed1996

Factors influencing the pharmacokinetics, dosimetry, and diagnostic accuracy of radioimmunodetection and radioimmunotherapy of carcinoembryonic antigen-expressing tumors.

The aim of this study was to examine factors that may influence the pharmacokinetics, diagnostic accuracy, and dosimetry in radioimmunodetection and radioimmunotherapy with anti-carcinoembryonic antigen (CEA) monoclonal antibodies (mAbs). Data from 275 patients with CEA expressing tumors were analyzed retrospectively. Of these, 69 patients devoid of human antimouse antibody (i.e., 31 colorectal, 9 lung, 7 breast, 4 ovarian, 6 pancreatic, 9 medullary thyroid, 1 gallbladder, and 1 salivary gland cancer, and 1 primary tumor of unknown origin) underwent a low-protein-dose diagnostic study (0.3-2.6 mg of protein; 6.8-28.8 mCi 131I-labeled IgG or fragments), followed within 4 weeks by a high-protein-dose therapy injection (4.0-27.5 mg of protein; 29.8-238.9 mCi). The anti-CEA antibodies NP-4 (Ka=10(8)M-1) and MN-14 (ka=10(9)M-1) were used. Plasma clearance, the molecular composition of radioactivity in the plasma, and the cumulated activity in organs and tumors were determined. Radiation doses were derived from the Medical Internal Radiation Dose scheme. At a low-protein dose and over a similar range of plasma CEA, a significantly higher percentage of MN-14 than of NP-4 was complexed with circulating CEA, consistent with its higher affinity. Complexation was reduced with increasing protein doses. However, the targeting sensitivity was not affected. Profound differences were found in the clearance of the antibody between different types of cancer. Colorectal cancer patients cleared the antibody significantly faster from blood (T1/2=17.6+/-12.6 versus 44.2 +/- 23.7 h) and whole body (t1/2= 53.2 +/- 30.1 versus 114.6+/-59.7 h) than all other tumor types (P <0.001). Consequently, significantly lower red marrow (2.1 +/- 1.0 cGy/mCi versus 4.3 +/- 1.6 cGy/mCi) and whole-body doses (0.5 +/- 0.3 cGy/mCi versus 1.0 +/- 0.4 cGy/mCi) were seen in colorectal cancer patients as compared with other tumor types (P < 0.001). This clearance is probably due to hepatic metabolism of the immune complexes. Clearance rates were especially high in patients with colorectal cancer having large liver metastases and elevated liver enzymes (rapid hepatic clearance with liberation of free I-). In contrast, a disease-stage and plasma CEA-matched cohort of colorectal cancer patients, examined with the 131 I-labeled anti-colon-specific antigen p mAb Mu-9, showed normal murine IgG pharmacokinetics (n=22;3 of them compared intraindividually to MN-14). Only in colorectal cancer patients did complexes between mAb and CEA tend to clear rapidly, whereas Mu-9 had normal kinetics in these patients. This suggests that different CEA-expressing cancer types may produce heterogeneous CEA molecules and that the variability in mAb clearance is due to varying clearance rates of these different circulating CEA subspecies. Disease-related alterations in antibody metabolism are unlikely, given that only anti-CEA antibodies exhibit this phenomenon.

Adolescent↗
PubMed1996

Gas chromatographic-mass spectrometric metabolic profiling of patients with fatal infantile mitochondrial myopathy with de Toni-Fanconi-Debré syndrome.

The metabolic profiles of three patients with fatal infantile mitochondrial myopathy with de Toni-Fanconi-Debré syndrome were studied by simultaneous analysis, after urease treatment of urinary organic acids, carbohydrates, polyols and amino acids using gas chromatography/mass spectrometry (GC/MS). All three patients persistently showed lactic aciduria, phosphaturia, glucosuria and generalized amino aciduria. This abnormal urinary metabolic profile was observed before the onset of any clinical symptoms, indicating that chemical diagnosis may be done presymptomatically. In one patient, the concentration of lactate increased in parallel with the severity of the clinical condition, whereas the urinary levels of 3-hydroxybutyrate, amino acids and glucose fluctuated and showed only a general tendency to increase with the clinical course. The above results suggest that simultaneous GC/MS analyses, without fractionation, of urinary metabolites facilitate not only the early chemical diagnosis either before or after the first onset, but also follow-up studies, providing an important index for the evaluation of the severity and clinical course in patients with this disorder.

Fanconi Syndrome↗
PubMed1996

Cloning, cDNA sequence, and alternative splicing of porcine amelogenin mRNAs.

In mammals, the organic matrix of developing enamel is dominated by amelogenins. To investigate the expression of proteins secreted into the developing enamel matrix, we have constructed a porcine enamel organ epithelia-specific cDNA library. The amelogenin fraction of the cDNA library was characterized by the cloning of amelogenin-specific polymerase chain-reaction (PCR) amplification products, 5' and 3' rapid amplification of cDNA ends (RACE), and by helper phage rescue of unamplified clones. Clones were characterized that encode porcine amelogenin isoforms 173, 157, 56, 41, and 40 amino acids in length. The structure of the porcine amelogenin gene differs from that of any of those yet described. There are two homologous but distinct exons 1, 2, and 7. One of the two exon 7s can vary in length depending upon the selection of either of two polyadenylation signal/cleavage sites. As a rule, a given exon 1 always pairs with the same exon 2 but can be associated with either exon 7. Despite significant sequence divergence within these exons, no differences are observed in exons 3, 5, and 6. We interpret these findings as evidence of a single amelogenin gene expressed from two promoters; however, the results do not exclude the existence of a second amelogenin gene. The variability generated through the use of alternate promoters and exon 7s primarily affects the non-coding regions of the message. A given amelogenin isoform expressed from the two promoters displays four amino acid differences within the signal peptide, while the secreted proteins are identical. Similarly, the alternative use of exon 7 does not alter the structure of the protein products. The pattern of RNA splicing of amelogenin pre-mRNAs is different for the transcripts expressed from the two promoters. The 173- and the 56-residue amelogenins can be expressed from either promoter, while the 157-residue amelogenin is generated by only one of the two promoters.

Alternative Splicing↗
PubMed1995

Gas chromatography-mass spectrometric studies of canine urinary metabolism.

After the urine was treated with urease, lyophilized, and trimethylsilylated, it was examined for metabolic profiles in Dalmatian dogs and Shetland sheepdogs by gas chromatography-mass spectrometry (GC/MS), which simultaneously analyzes organic acids, amino acids, sugars, sugar alcohols, purine and pyrimidine bases, and nucleosides. The profiles were compared with those from human specimens. As clarified in past studies, Dalmatian dogs showed an extreme decrease in allantoin, which is the final product of purine metabolism in the canine of other species, and a marked detection of uric acid peak. This finding suggests that purine metabolism in Dalmatian dogs is different from that in the other species. Only two Shetland sheepdogs, whose mother had chronic renal failure, showed a marked excretion of uric acid, as in Dalmatian dogs. In addition, some Dalmatian dogs, who were maintained on a protein-restricted diet, showed a little excretion of uric acid. A large amount of uric acid is detected in combination with pentose-monosaccharides, hexose-monosaccharides and sugar alcohols in neonatal human urine in comparison with the present dog samples. A marked difference between the canine and the humans is that phenylacetylglycine, which is derived from the aromatic amino acid phenylalanine, is excreted in the canine urine. Phenylacetylglycine is not detected in the human urine, and there have been no reports of its excretion in canine urine.

Amino Acids↗
PubMed1994

Correlation between monoclonal antibody reactivity and expression of CD4 and CD8 alpha genes in the horse.

Equine peripheral blood lymphocytes (PBL) were enriched by positive selection using panning with a mixture of monoclonal antibodies against putative equine CD4 (Equine Leucocyte Antigen Workshop antibodies WS 1 and WS 72), or CD8 molecules (Workshop antibodies WS 12, WS 49, and WS 74). RNA was extracted from CD4 enriched cells (99% purity), from CD8 enriched cells (69% purity), from peripheral blood lymphocytes, and from neonatal equine thymus. RNA extracted from equine granulocytes and from equine kidney served as negative control. The RNA was electrophoresed in agarose and transferred to nylon membranes. Northern blots were hybridized with human and mouse cDNA probes for CD4 and CD8 alpha. The human CD4 probe detected a 2.9 kb RNA transcript in equine PBL, CD4 enriched lymphocytes, and thymocytes. The human CD8 alpha probe detected a 2.0 kb transcript in RNA from equine CD8 alpha enriched lymphocytes and thymocytes, but not from PBL or CD4 enriched lymphocytes. Mouse cDNA probes for CD4 and CD8 did not react with equine RNA. Results of hybridizations using the human probes support the assignment of the CD4 and CD8 specificities to the antibodies listed above. The results also suggest that the equine CD4 and CD8 alpha genes are more closely related to the human than to the murine counterparts.

Animals↗
PubMed1994

Down-regulation followed by re-expression of equine CD4 molecules in response to phorbol myristate acetate.

The regulatory effects of phorbol myristate acetate (PMA) on the expression of the CD4 molecule on horse T cells were investigated. On both peripheral blood lymphocytes and thymocytes, PMA resulted in a rapid and transient down-regulation of equine CD4 expression, but had no such effect on the surface expression of equine CD5, CD8 or major histocompatibility complex (MHC) class I and class II molecules. Over 75% of the surface CD4 molecules per cell were lost after a 4 h exposure to PMA at 37 degrees C. The regulation of equine CD4 expression induced by PMA was temperature dependent and reversible. The PMA-mediated loss of CD4 expression was inhibited at 4 degrees C. After 24 h of exposure to PMA, CD4 molecules were re-expressed on the cell surface, even in the continued presence of PMA. These findings demonstrate that equine CD4+ T cells undergo alterations in CD4 expression in response to PMA, and suggest that the equine homolog of the CD4 molecule is regulated by PMA in a similar manner to the human CD4 molecule.

Animals↗