Abstract
The body's protective responses to infection, wounding, trauma, and malignancy include the acute-phase reaction, which is modulated by various cytokines and their cellular receptors. During the acute-phase reaction, levels of specific proteins synthesized by the liver increase in the plasma. Little information is available about the extrahepatic synthesis of plasma proteins during the acute-phase reaction. The study described here analyzes the tissue-specific expression of genes encoding the plasma proteins albumin (ALB), α1,-antitrypsin (AAT), transferrin (TF), haptoglobin (HP), ceruloplasmin (CP), serum amyloid A (SAA), α1-acid glycoprotein (AGP) and α2-HS-glycoprotein (AHSG) during the acute-phase reaction in C57B1 mice. The acute-phase reaction was induced by intraperitoneal injections of bacterial lipopolysaccharide (LPS). During the acute-phase reaction, genes encoding CP, SAA, AGP, and HP demonstrate unique extrahepatic tissue specific patterns of expression in kidney, spleen, thymus, heart, brain, lung, testis, and epididymis. Different temporal patterns of HP gene expression also were observed in lung and thymus after induction by LPS. The function of extrahepatic synthesis of plasma proteins is not yet understood; however, a local provision of specific plasma proteins in mammalian tissues may offer the host a source of functionally important proteins during periods of stress.
Similar content being viewed by others
References
Kushner, I., andA. Mackiewicz. 1987. Acute phase proteins as disease markers.Dis. Markers 5:1–11.
Adrian, G. S., D. C.Herbert, L. K.Robinson, C. A.Walter, J. M.Buchanan, E. K.Adrian, F. J.Weaker, C. A.Eddy, F.Yang, and B. H.Bowman. 1991. Expression of a human chimeric transferrin gene in senescent transgenic mice reflects the decrease of transferrin levels in aging humans (submitted).
Pepys, M. B., M. D. Baltz, K. Gomer, A. S. Davies, andM. Doenhoff. 1979. Serum amyloid P-component is an acute phase reactant in the mouse.Nature 278:259–261.
Lum, J. B., A. J. Infante, D. M. Marker, F. Yang, andB. H. Bowman. 1986. Transferrin synthesis by inducer T lymphocytes.J. Clin. Invest. 77:841–849.
Levin, M. J., D. Tuil, G. Uzan, J.-C. Dreyfus, andA. Kahn. 1984. Expression of the transferrin gene during development of nonhepatic tissues: High level of transferrin mRNA in fetal muscle and adult brain.Biochem. Biophys. Res. Commun. 122:212–217.
Aldred, A. R., A. Grimes, G. Schreiber, andJ. F. B. Mercer. 1987. Rat ceruloplasmin. Molcular cloning and gene expression in liver, choroid plexus, yolk sac, placenta and testis.J. Biol. Chem. 262:2875–2878.
Skinner, M. K., andM. D. Griswold. 1983. Sertoli cells synthesize and secrete a ceruloplasmin-like protein.Biol. Reprod. 28:1225–1229.
Dickson, P. W., A. R. Aldred, P. D. Marley, G. F. Tu, G. J. Howlett, andG. Schreiber. 1985. High prealbumin and transferrin mRNA levels in the choroid plexus of rat brain.Biochem. Biophys. Res. Commun. 127:890–895.
Ruther, U., M. Tripodi, R. Cortese, andE. F. Wagner. 1987. The human alpha-1-antitrypsin gene is efficiently expressed from two tissue specific promoters in transgenic mice.Nucleic Acids Res. 15:7519–7529.
Kelsey, G. D., S. Povey, A. E. Bygrave, andR. H. Lovell-Badge. 1987. Species and tissue-specific expression of human alpha-1-antitrypsin in transgenic mice.Genes Dev. 1:161–171.
Koopman, P., S. Povey, andR. H. Lovell-Badge. 1989. Widespread expression of humanα 1-antitrypsin in transgenic mice revealed by in situ hybridization.Genes Dev. 3:16–25.
Schreiber, G., A. Tsykin, A. R. Aldred, T. Thomas, Wai-Ping Fung, P. W. Dickson, T. Cole, H. Birch, F. A. De Jong, andJ. Milland. 1989. The acute phase response in the rodent.Ann. N.Y. Acad. Sci. 557:61–86.
Meek, R. L., andE. P. Benditt. 1986. Amyloid A gene family expression in different mouse tissues.J. Exp. Med. 164:2006–2017.
Katz, Y., M. Revel, andR. C. Struck. 1989. Interleukin 6 stimulates synthesis of complement proteins factor B and C3 in human skin fibroblasts.Eur. J. Immunol. 19:983–988.
Chomczynski, P., andN. Sacchi. 1987. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.Anal. Biochem. 162:156–159.
Fourney, R. M., J. Miyakoshi, R. S. Day, III andM. C. Paterson. 1988. Northern blotting: Efficient RNA staining and transfer.Focus (Bethesda Res. Lab.) 10:5–7.
Leharch, H., D. Diamond, J. M. Wozney, andH. Boedtker. 1977. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination.Biochemistry 16:4743–4751.
Davies, L. G., M. D. Dibner, andJ. F. Battey. 1986. InBasic Methods in Molecular Biology. Elsevier Science Publishing, New York, 143–149.
Feinberg, A. P., andB. Vogelstein. 1983. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity.Anal. Biochem. 132:6–13.
Yang, F., J. L. Brune, W. D. Baldwin, D. R. Barnett, andB. H. Bowman. 1983. Identification and characterization of human haptoglobin cDNA.Proc. Natl. Acad. Sci. U.S.A. 80:5875–5879.
Yang, F., J. B. Lum, J. R. McGill, C. M. Moore, S. L. Naylor, P. H. Van Bragt, W. D. Baldwin, andB. H. Bowman. 1984. Human transferrin: cDNA characterization and chromosomal localization.Proc. Natl. Acad. Sci. U.S.A. 81:2752–2756.
Yang, F., S. L. Naylor, J. B. Lum, S. Cutshaw, J. L. McCombs, K. H. Naberhaus, J. R. McGill, G. S. Adrian, C. M. Moore, D. R. Barnett, andB. H. Bowman. 1986. Characterization, mapping and expression of human ceruloplasmin gene.Proc. Natl. Acad. Sci. U.S.A. 83:3257–3261.
Yang, F., Z.-L.Chen, J. M.Bergeron, R. L.Cupples, and W. E.Friedrichs. 1991. Human alpha-2-HS-gylcoprotein/bovine fetuin homologue in mice: Identification of the cDNA sequence and developmertal regulation of the gene (submitted).
Yamamoto, K.-I., andS. Migita. 1985. Complete primary structures of two major murine serum amyloid A proteins deduced from cDNA sequences.Proc. Natl. Acad. Sci. U.S.A. 82:2915–2919.
Lee, S.-C., C.-J. Chang, Y.-M. Lee, H.-Y. Lei, M.-Y. Lai, andD.-S. Chen. 1989. Molecular cloning of cDNAs corresponding to two genes of alpha-1-acid glycoprotein and characterization of two alleles of alpha-1-acid glycoprotein in the mouse.DNA 8(4):245–251.
Sifers, R. N., F. D. Ledley, L. Reed-Fourquet, D. H. Ledbetter, S. A. Ledbetter, andS. L. C. Woo. 1990. Complete cDNA sequence and chromosomal localization of mouse alpha1-antitrypsin.Genomic 6:100–104.
Draper, N. R., andH. Smith. 1966. Applied Regression Analysis. John Wiley & Sons, New York. 77–81.
Yang, F., W. E. Friedrichs, J. M. Buchanan, D. C. Herbert, F. J. Weaker, J. H. Brock, andB. H. Bowman. 1990. Tissue specific expression of mouse transferrin during development and aging.Mech. Age. Dev. 56:187–197.
Lang, C. H., G. J. Bagby, andJ. J. Spitzer. 1985. Glucose kinetics and body temperature after lethal and nonlethal doses of endotoxin.Ann. J. Physiol. 248:R471-R478.
Filkins, J. P. andN. R. Diluzio. 1968. Endotoxin induced hypothermia and tolerance in the rat.Proc. Soc. Exp. Biol Med. 129:724–726.
Inarrea, P., J. Cambronero-Gonez, J. Pascual, M. Del C. Ponte, L. Herando, andM. Sanchez-Crespo. 1985. Synthesis of PAF-acether and blood volume changes in gram-negative sepsis.Immunopharmacology 9:45–52.
Baumhueter, S., D. B. Mendel, P. B. Conley, C. J. Kuo, C. Turk, M. K. Graves, C. A. Edwards, G. Courtois, andG. R. Crabtree. 1990. HNF-1 shares three sequence motifs with the POU domain proteins and is identical to LB-B1 and APF.Genes Dev. 4:372–379.
Author information
Authors and Affiliations
Additional information
Supported in part by NIH grants GM33298, AG0672, and AG06650 and a fellowship to N.K. from the Educational Commission for Foreign Medical Graduates, Philadelphia.
Rights and permissions
About this article
Cite this article
Kalmovarin, N., Friedrichs, W.E., O'brien, H.V. et al. Extrahepatic expression of plasma protein genes during inflammation. Inflammation 15, 369–379 (1991). https://doi.org/10.1007/BF00917353
Issue Date:
DOI: https://doi.org/10.1007/BF00917353