alpha globulins


Summary: Serum proteins that have the most rapid migration during ELECTROPHORESIS. This subgroup of globulins is divided into faster and slower alpha(1)- and alpha(2)-globulins.

Top Publications

  1. Sanggaard K, Karring H, Valnickova Z, Thøgersen I, Enghild J. The TSG-6 and I alpha I interaction promotes a transesterification cleaving the protein-glycosaminoglycan-protein (PGP) cross-link. J Biol Chem. 2005;280:11936-42 pubmed
    ..An intermediate is formed resulting in a partitioning of the reaction between HC(1 or 2).TSG-6 complexes and transfer of HC(1 or 2) to the chondroitin via competing pathways. ..
  2. Jarup L, Hellstrom L, Alfven T, Carlsson M, Grubb A, Persson B, et al. Low level exposure to cadmium and early kidney damage: the OSCAR study. Occup Environ Med. 2000;57:668-72 pubmed
    ..0 nmol/mmol creatinine. Renal tubular damage due to exposure to cadmium develops at lower levels of cadmium body burden than previously anticipated. ..
  3. Werbowetski Ogilvie T, Agar N, Waldkircher de Oliveira R, Faury D, Antel J, Jabado N, et al. Isolation of a natural inhibitor of human malignant glial cell invasion: inter alpha-trypsin inhibitor heavy chain 2. Cancer Res. 2006;66:1464-72 pubmed
  4. Diarra Mehrpour M, Sarafan N, Bourguignon J, Bonnet F, Bost F, Martin J. Human inter-alpha-trypsin inhibitor heavy chain H3 gene. Genomic organization, promoter analysis, and gene linkage. J Biol Chem. 1998;273:26809-19 pubmed
    ..The latter factors control the transcription of the ITIH3 gene positively. ..
  5. Paris S, Sesboué R, Delpech B, Chauzy C, Thiberville L, Martin J, et al. Inhibition of tumor growth and metastatic spreading by overexpression of inter-alpha-trypsin inhibitor family chains. Int J Cancer. 2002;97:615-20 pubmed
    ..In vitro, ITI-L expression significantly decreased chemotaxis and ITI-HI and ITI-H3 expression increased cell attachment. These results argue for the antitumoral or antimetastatic properties of ITI-L, -HI and -H3 chains. ..
  6. Rugg M, Willis A, Mukhopadhyay D, Hascall V, Fries E, Fulop C, et al. Characterization of complexes formed between TSG-6 and inter-alpha-inhibitor that act as intermediates in the covalent transfer of heavy chains onto hyaluronan. J Biol Chem. 2005;280:25674-86 pubmed
    ..The finding that TSG-6 acts as cofactor and catalyst in the production of HC x HA complexes has important implications for our understanding of inflammatory and inflammation-like processes. ..
  7. Wisniewski H, Hua J, Poppers D, Naime D, Vilcek J, Cronstein B. TNF/IL-1-inducible protein TSG-6 potentiates plasmin inhibition by inter-alpha-inhibitor and exerts a strong anti-inflammatory effect in vivo. J Immunol. 1996;156:1609-15 pubmed
  8. Zhuo L, Hascall V, Kimata K. Inter-alpha-trypsin inhibitor, a covalent protein-glycosaminoglycan-protein complex. J Biol Chem. 2004;279:38079-82 pubmed
  9. De La Motte C, Hascall V, Drazba J, Bandyopadhyay S, Strong S. Mononuclear leukocytes bind to specific hyaluronan structures on colon mucosal smooth muscle cells treated with polyinosinic acid:polycytidylic acid: inter-alpha-trypsin inhibitor is crucial to structure and function. Am J Pathol. 2003;163:121-33 pubmed

More Information


  1. Lim Y, Bendelja K, Opal S, Siryaporn E, Hixson D, Palardy J. Correlation between mortality and the levels of inter-alpha inhibitors in the plasma of patients with severe sepsis. J Infect Dis. 2003;188:919-26 pubmed
    ..Thus, human IalphaIp may be a useful predictive marker and potential therapeutic agent in sepsis. ..
  2. Opal S, Lim Y, Siryaporn E, Moldawer L, Pribble J, Palardy J, et al. Longitudinal studies of inter-alpha inhibitor proteins in severely septic patients: a potential clinical marker and mediator of severe sepsis. Crit Care Med. 2007;35:387-92 pubmed
    ..Inter-alpha inhibitor proteins are markedly reduced in severe sepsis, and failure of recovery of IalphaIp levels over the course of sepsis is associated with an unfavorable outcome. ..
  3. Zhuo L, Salustri A, Kimata K. A physiological function of serum proteoglycan bikunin: the chondroitin sulfate moiety plays a central role. Glycoconj J. 2002;19:241-7 pubmed
    ..Therefore, the chondroitin sulfate moiety of bikunin is essential for presenting SHAP to hyaluronan, which is indispensable for ovulation and fertilization in mammals. ..
  4. Jessen T, Ødum L. Role of tumour necrosis factor stimulated gene 6 (TSG-6) in the coupling of inter-alpha-trypsin inhibitor to hyaluronan in human follicular fluid. Reproduction. 2003;125:27-31 pubmed
    ..In conclusion, TSG-6 is necessary for the coupling of ITI to hyaluronan, but at least one additional component in follicular fluid is essential. ..
  5. Mukhopadhyay D, Asari A, Rugg M, Day A, Fulop C. Specificity of the tumor necrosis factor-induced protein 6-mediated heavy chain transfer from inter-alpha-trypsin inhibitor to hyaluronan: implications for the assembly of the cumulus extracellular matrix. J Biol Chem. 2004;279:11119-28 pubmed
  6. Jessen T, Ødum L. TSG-6 and calcium ions are essential for the coupling of inter-alpha-trypsin inhibitor to hyaluronan in human synovial fluid. Osteoarthritis Cartilage. 2004;12:142-8 pubmed
    ..Tumor necrosis factor stimulated gene 6 (TSG-6) and calcium ions are both essential for the coupling of inter-alpha-trypsin inhibitor to hyaluronan in human synovial fluid. ..
  7. Yang S, Lim Y, Zhou M, Salvemini P, Schwinn H, Josic D, et al. Administration of human inter-alpha-inhibitors maintains hemodynamic stability and improves survival during sepsis. Crit Care Med. 2002;30:617-22 pubmed
    ..Human IalphaI/PalphaI appears to be a useful agent for maintaining hemodynamic stability and improving survival during the progression of polymicrobial sepsis. ..
  8. Opal S, Artenstein A, Cristofaro P, Jhung J, Palardy J, Parejo N, et al. Inter-alpha-inhibitor proteins are endogenous furin inhibitors and provide protection against experimental anthrax intoxication. Infect Immun. 2005;73:5101-5 pubmed
    ..001). We conclude that human IalphaIp may be an effective preventative or therapeutic agent against anthrax intoxication. ..
  9. Holdt Lehmann B, Lehmann A, Korten G, Nagel H, Nizze H, Schuff Werner P. Diagnostic value of urinary alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase in comparison to alpha 1-microglobulin as a marker in evaluating tubular dysfunction in glomerulonephritis patients. Clin Chim Acta. 2000;297:93-102 pubmed
    ..AAP indicates very early tubular impairment and, in some cases, AAP is elevated although NAG and a1M are still within normal ranges. We suggest that the enzyme activities are useful in the diagnostics of early stages of the disease. ..
  10. Diarra Mehrpour M, Bourguignon J, Sesboue R, Mattei M, Passage E, Salier J, et al. Human plasma inter-alpha-trypsin inhibitor is encoded by four genes on three chromosomes. Eur J Biochem. 1989;179:147-54 pubmed
    ..The light-chain gene is located in the q32-q33 region of chromosome 9. These results indicate that heavy and light chains of inter-alpha-trypsin inhibitor are encoded by at least four functional genes. ..
  11. Bost F, Diarra Mehrpour M, Martin J. Inter-alpha-trypsin inhibitor proteoglycan family--a group of proteins binding and stabilizing the extracellular matrix. Eur J Biochem. 1998;252:339-46 pubmed
    ..We will focus on the heavy chain linkage with HA, which represents the demonstration of covalent binding between proteins and HA. ..
  12. Mizushima S, Nii A, Kato K, Uemura A. Gene expression of the two heavy chains and one light chain forming the inter-alpha-trypsin-inhibitor in human tissues. Biol Pharm Bull. 1998;21:167-9 pubmed
    ..These results suggest the possibility that the major tissue which produces ITI is the liver, and the H chains and L chain (UTI) are produced as a component of ITI- related proteins in other tissues as well as in the liver. ..
  13. Choi Miura N, Sano Y, Oda E, Nakano Y, Tobe T, Yanagishita T, et al. Purification and characterization of a novel glycoprotein which has significant homology to heavy chains of inter-alpha-trypsin inhibitor family from human plasma. J Biochem. 1995;117:400-7 pubmed
    ..We designated GP120 as IHRP (ITI heavy chain-related protein). ..
  14. Gebhard W, Schreitmüller T, Hochstrasser K, Wachter E. Two out of the three kinds of subunits of inter-alpha-trypsin inhibitor are structurally related. Eur J Biochem. 1989;181:571-6 pubmed
    ..Therefore, we conclude that the deduced primary structure covers about 98% of the mature third subunit. ..
  15. Huang L, Yoneda M, Kimata K. A serum-derived hyaluronan-associated protein (SHAP) is the heavy chain of the inter alpha-trypsin inhibitor. J Biol Chem. 1993;268:26725-30 pubmed
    ..NH2-terminal sequences of the fragments suggested the participation of the COOH-terminal half of ITI with an amphipathic alpha helix structure in the HA binding. ..
  16. Takeyoshi M, Mitoma H, Yamasaki K. Changes in serum alpha2u-globulin levels in castrated male rats treated with testosterone propionate in a Hershberger assay. J Appl Toxicol. 2005;25:176-8 pubmed
  17. Roebroek A, Taylor N, Louagie E, Pauli I, Smeijers L, Snellinx A, et al. Limited redundancy of the proprotein convertase furin in mouse liver. J Biol Chem. 2004;279:53442-50 pubmed
  18. Enghild J, Thøgersen I, Cheng F, Fransson L, Roepstorff P, Rahbek Nielsen H. Organization of the inter-alpha-inhibitor heavy chains on the chondroitin sulfate originating from Ser(10) of bikunin: posttranslational modification of IalphaI-derived bikunin. Biochemistry. 1999;38:11804-13 pubmed
    ..Taken together, the data show the following organization of the IalphaI molecule: [GlcUA-GalNAc](a)-HC1-[GlcUA-GalNAc](b)-HC2-[GlcUA-GalNAc](c)-Gal -Gal-Xyl-Ser(10)-bikunin, (a + b + c = 12-18 disaccharides). ..
  19. Doi A, Hill G, Seely J, Hailey J, Kissling G, Bucher J. alpha 2u-globulin nephropathy and renal tumors in national toxicology program studies. Toxicol Pathol. 2007;35:533-40 pubmed
  20. Li X, Miyajima M, Mineki R, Taka H, Murayama K, Arai H. Analysis of potential diagnostic biomarkers in cerebrospinal fluid of idiopathic normal pressure hydrocephalus by proteomics. Acta Neurochir (Wien). 2006;148:859-64; discussion 864 pubmed
    ..In particular, the CSF level assay of LRG suggests that LRG is a specific biomarker for INPH and has potential use in the diagnosis and indication for CSF shunting. ..
  21. Penders J, Delanghe J. Alpha 1-microglobulin: clinical laboratory aspects and applications. Clin Chim Acta. 2004;346:107-18 pubmed
  22. Soury E, Olivier E, Daveau M, Hiron M, Claeyssens S, Risler J, et al. The H4P heavy chain of inter-alpha-inhibitor family largely differs in the structure and synthesis of its prolin-rich region from rat to human. Biochem Biophys Res Commun. 1998;243:522-30 pubmed
    ..Therefore, in contrast to what is seen for the ITIH1 to -3 genes, the rat and human ITIH4 gene transcriptions and products thereof present marked differences, which suggests species-specific functions for I alpha IH4P. ..
  23. Surjit M, Oberoi R, Kumar R, Lal S. Enhanced alpha1 microglobulin secretion from Hepatitis E virus ORF3-expressing human hepatoma cells is mediated by the tumor susceptibility gene 101. J Biol Chem. 2006;281:8135-42 pubmed
    ..These results suggest a mechanism by which the ORF3 protein exploits the endosomal sorting machinery to enhance the secretion of an immunosuppressant molecule (alpha1 microglobulin) from the cultured hepatocytes. ..
  24. Alavi Shoushtari S, Asri Rezai S, Abshenas J. A study of the uterine protein variations during the estrus cycle in the cow: a comparison with the serum proteins. Anim Reprod Sci. 2006;96:10-20 pubmed
    ..During the follicular phase of the cycle uterine alpha globulins are higher than those in other phases, with an elevation in beta1 and a reduction in beta2 and gamma globulin ..
  25. Coe J, Vomachka A, Ross M. Effect of hamster pregnancy on female protein, a homolog of serum amyloid P component. Proc Soc Exp Biol Med. 1999;221:369-75 pubmed
  26. Machii R, Sakatume M, Kubota R, Kobayashi S, Gejyo F, Shiba K. Examination of the molecular diversity of alpha1 antitrypsin in urine: deficit of an alpha1 globulin fraction on cellulose acetate membrane electrophoresis. J Clin Lab Anal. 2005;19:16-21 pubmed
    ..Detecting changes in alpha1G fractions in CAE may support the differential diagnosis of IgAN from other types of GN. ..
  27. Josic D, Brown M, Huang F, Lim Y, Rucevic M, Clifton J, et al. Proteomic characterization of inter-alpha inhibitor proteins from human plasma. Proteomics. 2006;6:2874-85 pubmed
    ..The importance of the application of proteomic methods for the proper evaluation of therapeutic drugs based on human plasma is discussed. ..
  28. Holm J, Ravn J, Ingemann Hansen S. Urinary excretion of alpha1-microglobulin and albumin in acute myocardial infarction. Correlation with plasma concentrations of troponin I and C-reactive protein. Scand J Urol Nephrol. 2006;40:339-44 pubmed
    ..Extrarenal inflammatory processes seem to affect renal tubular function, thereby contributing to microalbuminuria during MI. ..
  29. Sanggaard K, Scavenius C, Rasmussen A, Wisniewski H, Thøgersen I, Enghild J. The TSG-6/HC2-mediated transfer is a dynamic process shuffling heavy chains between glycosaminoglycans. J Biol Chem. 2010;285:21988-93 pubmed publisher
    ..The results demonstrate reversibility of the interactions between HCs and glycosaminoglycans and suggest that a dynamic shuffling of the HCs occur in vivo. ..
  30. Fraser J, Muller A, Smith D, Newman D, Lamb E. Renal tubular injury is present in acute inflammatory bowel disease prior to the introduction of drug therapy. Aliment Pharmacol Ther. 2001;15:1131-7 pubmed
    ..Tubular proteins are not useful predictors of an adverse renal response to 5-ASA. Serum cystatin C may be an improved marker of glomerular filtration rate in this setting. ..
  31. Salier J, Chan P, Raguenez G, Zwingman T, Erickson R. Developmentally regulated transcription of the four liver-specific genes for inter-alpha-inhibitor family in mouse. Biochem J. 1993;296 ( Pt 1):85-91 pubmed
  32. Matrosovich M, Zhou N, Kawaoka Y, Webster R. The surface glycoproteins of H5 influenza viruses isolated from humans, chickens, and wild aquatic birds have distinguishable properties. J Virol. 1999;73:1146-55 pubmed
  33. Ekstrom B, Berggard I. Human alpha1-microglobulin. Purification procedure, chemical and physiochemical properties. J Biol Chem. 1977;252:8048-57 pubmed
  34. Schaub S, Nickerson P, Rush D, Mayr M, Hess C, Golian M, et al. Urinary CXCL9 and CXCL10 levels correlate with the extent of subclinical tubulitis. Am J Transplant. 2009;9:1347-53 pubmed publisher
    ..002), but only tubular injury markers were elevated in IF/TA. These results demonstrate a correlation of urinary CXCL9 and CXCL10 levels with the extent of subclinical tubulitis suggesting potential as noninvasive screening biomarkers. ..
  35. Ochsner S, Russell D, Day A, Breyer R, Richards J. Decreased expression of tumor necrosis factor-alpha-stimulated gene 6 in cumulus cells of the cyclooxygenase-2 and EP2 null mice. Endocrinology. 2003;144:1008-19 pubmed
    ..These observations identify TSG-6 as a target of PG action and show that its production in ovulatory follicles is associated with proper formation of the cumulus-derived extracellular matrix. ..
  36. Shihabi Z. Analysis of immune complexes by capillary electrophoresis. Electrophoresis. 2008;29:2565-9 pubmed publisher
    ..It also reveals the composition (monoclonality) of the precipitate. Three types of IC have been detected in this method: monoclonal, polyclonal and mixed (mono-polyclonal) IC. Furthermore, the method is rapid and simple. ..
  37. Matsumoto S, Ding L, Ishii M, Fischer N, Inaba T. The interaction of human and bovine serum proteins with CYP3A in human liver microsomes: inhibition of testosterone 6beta-hydroxylation by albumin, alpha-globulins, alpha(1)-acid glycoprotein and gamma-globulins. Toxicol Lett. 2002;136:33-41 pubmed
    ..Since the bovine serum proteins showed weaker inhibitory effects than human serum proteins, the wide use of BSA, which is viewed as interchangeable with HSA, needs to be cautioned. ..
  38. Ricchiuti V, Hartke D, Yang L, Goldman H, Elder J, Resnick M, et al. Levels of urinary inter-alpha-trypsin inhibitor trimer as a function of age and sex-hormone status in males and females not forming stones. BJU Int. 2002;90:513-7 pubmed
  39. Wang J, Aasen A. Is inter-alpha inhibitor important in sepsis?. Crit Care Med. 2007;35:634-5 pubmed
  40. Ishii M, Xu B, Ding L, Fischer N, Inaba T. Interaction of plasma proteins with cytochromes P450 mediated metabolic reactions: inhibition by human serum albumin and alpha-globulins of the debrisoquine 4-hydroxylation (CYP2D) in liver microsomes of human, hamster and rat. Toxicol Lett. 2001;119:219-25 pubmed
    ..Since the observed inhibition is inconsistent with level of protein binding, it appears, particularly in the case of alpha-globulins, that the plasma proteins interact with CYP2D directly. ..
  41. Ferguson L, Lebetkin E, Lih F, Tomer K, Parkinson H, Borghoff S, et al. 14C-labeled pulegone and metabolites binding to alpha2u-globulin in kidneys of male F-344 rats. J Toxicol Environ Health A. 2007;70:1416-23 pubmed
    ..However, binding of pulegone and/or metabolites to alpha2u-globulin did not produce accumulation of this protein in the kidney. ..
  42. Lindqvist A, Bratt T, Altieri M, Kastern W, Akerstrom B. Rat alpha 1-microglobulin: co-expression in liver with the light chain of inter-alpha-trypsin inhibitor. Biochim Biophys Acta. 1992;1130:63-7 pubmed
    ..Free alpha 1-microglobulin and a polyprotein, containing both alpha 1-microglobulin and inter-alpha-trypsin inhibitor epitopes, were found in the microsomal fraction from rat liver homogenates. ..
  43. Short B. Cell proliferation and renal carcinogenesis. Environ Health Perspect. 1993;101 Suppl 5:115-20 pubmed
    ..An exciting recent finding is altered expression of transforming growth factor-alpha in hereditary rat renal cell carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  44. Dill J, Fuciarelli A, Lee K, Mellinger K, Chan P, Burka L, et al. Single administration toxicokinetic studies of decalin (decahydronaphthalene) in rats and mice. Toxicol Sci. 2003;72:210-22 pubmed
    ..0. Therefore, alpha2u-globulin was a key factor in the accumulation of decalin and decalone in kidneys of young male rats, decalin and decalone were practically absent in all females and in old males. ..
  45. Korinthenberg R, Sager J, Zimmerhackl L. Increased urinary excretion of tubular enzymes and proteins in children with epilepsy. Eur J Paediatr Neurol. 2000;4:263-7 pubmed
    ..While the cause is unknown, the influence of serotonin metabolism is discussed. ..
  46. Borghoff S, Prescott J, Janszen D, Wong B, Everitt J. alpha 2u-Globulin nephropathy, renal cell proliferation, and dosimetry of inhaled tert-butyl alcohol in male and female F-344 rats. Toxicol Sci. 2001;61:176-86 pubmed
    ..Together these data suggest that TBA causes alpha 2u-N in male rats, which is responsible for the male rat-specific increase in renal cell proliferation. ..
  47. Getting S, Mahoney D, Cao T, Rugg M, Fries E, Milner C, et al. The link module from human TSG-6 inhibits neutrophil migration in a hyaluronan- and inter-alpha -inhibitor-independent manner. J Biol Chem. 2002;277:51068-76 pubmed
  48. Xu B, Ishii M, Ding L, Fischer N, Inaba T. Interaction of serum proteins with CYP isoforms in human liver microsomes: inhibitory effects of human and bovine albumin, alpha-globulins, alpha-1-acid glycoproteins and gamma-globulins on CYP2C19 and CYP2D6. Life Sci. 2003;72:1953-62 pubmed
    ..A direct interaction of these serum proteins with CYP enzymes is postulated. Differential effects of bovine and human serum proteins and CYP specific inhibition were observed. ..
  49. Machii R, Matsuda K, Hiratsuka N, Sugimoto K, Hotta O, Itoh Y, et al. Analysis of an expanded width of albumin fraction by cellulose acetate membrane electrophoresis in IgA nephropathy urine before treatment. J Clin Lab Anal. 2003;17:37-43 pubmed
    ..This suggests that the characteristic expanded width of albumin found by immunofixation indicates a THP-albumin complex, and that the sodium concentration of urine is involved in the formation of this complex. ..
  50. Tavakkol A. Molecular cloning of porcine alpha 1-microglobulin/HI-30 reveals developmental and tissue-specific expression of two variant messenger ribonucleic acids. Biochim Biophys Acta. 1991;1088:47-56 pubmed
  51. Kew M. Abelev GI, Assecritova IG, Kraevsky NA, Perova SD, Perevodchikova NI. Embryonal serum alpha-globulin in cancer patients. Diagnostic value [Int J Cancer 1967;2:551-558]. J Hepatol. 2002;37:172-5 pubmed
  52. Allhorn M, Klapyta A, Akerstrom B. Redox properties of the lipocalin alpha1-microglobulin: reduction of cytochrome c, hemoglobin, and free iron. Free Radic Biol Med. 2005;38:557-67 pubmed
    ..The redox properties of alpha1m may provide a physiological protection mechanism against extracellularly exposed heme groups and other oxidants. ..
  53. González Rodríguez J, Canalejo D, Martín Govantes J, García de Guadiana L, Rex C, Gonzalez Morales M, et al. [Proteinuria in urinary infection and acute pyelonephritis in paediatric patients: can it replace scintigraphic studies in diagnostic localisation?]. Nefrologia. 2009;29:163-9 pubmed publisher
    ..The combined use of different urinary markers of renal function does not increase its sensitivity. It is necessary to do research in order to confirm the utility of new biomarkers. ..