Leukocyte surface origin of human alpha1-acid glycoprotein (orosomucoid).

Abstract

Human al-acid glycoprotein (orosomucoid) (o~I-AG) 1 constitutes the main component of the seromucoid fraction of human plasma. It belongs to the acute phase proteins, which increase under conditions such as inflammation, pregnancy, and cancer (1, 2). al-AG has previously been found to be synthesized in liver (3), and after removal of terminal sialic acids, it is cleared from the circulation by binding to a receptor protein on liver cell plasma membranes (4).The structure of al-AG is well known. It is composed of a single polypeptide chain and contains 245% carbohydrate including a large amount of sialic acid. The carbohydrate is located in the first half of the peptide chain linked to asparagine residues (5, 6).The function of al-AG is unclear. However, Schmid et al. (5) and Ikenaka et al. (7) and reported that the amino acid sequence of the protein shows a significant homology with human IgG. This finding and the striking increase in inflammatory and lymphoproliferative disorders made us consider the possibility that leukocytes could be directly involved in the synthesis and release of a~-AG.We report here the presence of a membrane form of al-AG, with an apparent tool wt of 52,000, on normal human lymphocytes, granulocytes, and monocytes. By the use of internal labeling with [3H]leucine in vitro, we demonstrate that the membrane protein is synthesized by lymphocytes. It is apparently subsequently cleaved and released as the soluble serum form with the normal tool wt of 41,000. Materials and MethodsIsolation of az-AG, aI-AG was isolated from the urine of patients with acute infectious mononucleosis by modifications of previously published methods (8). 6 liters of urine were collected, dialyzed against tap water overnight, and lyophilized. The powder was dissolved in 0.02 M sodium phosphate, pH 7.2, and applied to a 50-ml column of DEAE-cellulose made in the same buffer. After washing, a linear 200-ml gradient of 0.02 M sodium phosphate (200 ml of 1 M NaC1, 0.02 M sodium phosphate) was applied. The a~-AG-containing fractions, which were identified by polyacrylamide slab gel electrophoresis, eluted with an NaC1 concentration of 0.05-0.15 M. These were combined, dialyzed against water, and lyophilized. The powder was dissolved in 95 ml of * Supported by the Academy of Finland, the Finnish Cancer Society, and the Sigrid Jusdlius Stiftelse.Abbreviations used in this paper: ~-AG, al-acid glycoprotein; AET, 2-amino ethylisothiouronium bromide; buffer A, 0.15 M NaC1, 0.01 M sodium phosphate pH 7.4, 1% Triton X-100, 2 mM phenyl methyl sulfonyl fluoride, 1% ethanol; CNBr, cyanogen bromide; FITC, fluorescein isothiocyanate, LBL, lymphoblastoid B-cell line; MGG, May-Gruenwald-Giemsa stain; MLC, mixed lymphocyte culture; PBS, 0.15 M NaC1, 0.01 M sodium phosphate, pH 7.4; SDS, sodium dodecyl sulfate; SRBC, sheep erythrocytes. J. Exp. MEv.

Utility of C‐reactive protein and serum amyloid A in the diagnosis of equine protozoal myeloencephalitis

“…An increase in CRP concentration in CSF is thought to largely result from blood‐brain barrier damage (ex. subarachnoid hemorrhage6 or vasculitis due to sepsis17); intrathecal production of CRP18 and disruption of glymphatic circulation may also contribute to a lesser extent 19. Even when the blood–brain barrier is intact CRP level in the CSF is directly related to serum CRP because this protein flows from blood into the cerebrospinal space,20 but determination of a CRP index along with IgG index has been proposed in cases of canine Steroid Responsive Meningitis‐Arteritis (SRMA)6 and may also be helpful in cases of blood–brain barrier disruption in equine neurological disease.…”

Modulation of α1-acid glycoprotein (AGP) gene induction following honey bee venom administration to adjuvant arthritic (AA) rats; possible role of AGP on AA development

“…or is significantly reduced when AA is suppressed by several drugs (Figs 1 and 3) [26]. Membrane-bound AGP has been found on normal human lymphocytes, granulocytes and monoeytes [3]. and was also found to play a distinct positive [5] role in T cell activation process, or lo interfere wiih phagocytosis of bacteria by macrophages [4].…”

“…However, il is believed that AGP is involved in ihc regulation of Ihc immune system. AGP has been reported to be present on the surface membrane of normal human lymphocytes, granulocytes and monoeytes [3]. to interfere with phagocytosis of bacteria by macrophages [4.5].…”

Alpha 1 Acid Glycoprotein: Increased Serum and Localized mRNA Expression as a Monitor for Reactions in Leprosy

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