Characterization of recombinant type II collagen

Arthritogenicity and tolerogenicity in DBA/1 mice

Linda Myers, David Brand, X. J. Ye, M. A. Cremer, E. F. Rosloniec, M. Bodo, J. Myllyharju, T. Helaakoski, M. Nokelainen, T. Pihlajaniemi, K. Kivirikko, C. L. Yang, L. Alakokko, D. J. Prockop, H. Notbohm, P. Fietzek, John Stuart, Andrew Kang

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Recombinant human type II collagen (rhCII) was produced using both the HT1080 mammalian cell expression system (rhCII(ht)) and a baculovirus expression system (rhCII(bac)). The biosynthesis of CII requires extensive post-translational modifications, such as the hydroxylation of prolyl and lysyl residues and glycosylation of hydroxylysyl residues. Amino acid analyses indicated that the rhCII(bac) was adequately hydroxylated at prolyl residues but underhydroxylated at lysyl residues and underglycosylated compared with tissue-derived hCII, while rhCII(ht) was hyperhydroxylated and hyperglycosylated at lysyl residues. When the murine collagen-induced arthritis (CIA) model was used to investigate the immunological properties of the two forms of recombinant CII, each induced a high incidence of arthritis following immunization of susceptible mice when emulsified with complete Freund's adjuvant (CFA). However, the severity of the arthritis, as assessed by the number of affected limbs, was significantly higher in mice immunized with rhCII(ht) than in mice immunized with rhCII(bac). These data indicate that the degree of hydroxylysine glycosylation may play a role in the induction of the arthritogenic response to CII. Each of the recombinant collagens was comparable to tissue-derived hCII in their ability to induce tolerance and suppress arthritis when given as intravenous or oral tolerogens. Taken together, our data suggest that recombinant CII can be prepared in adequate amounts for therapeutic uses and that the material is immunologically comparable to tissue-derived hCII when used to induce tolerance.

Original languageEnglish (US)
Pages (from-to)631-639
Number of pages9
JournalImmunology
Volume95
Issue number4
DOIs
StatePublished - Dec 21 1998

Fingerprint

Inbred DBA Mouse
Collagen Type II
Arthritis
Glycosylation
Hydroxylysine
Experimental Arthritis
Freund's Adjuvant
Baculoviridae
Therapeutic Uses
Hydroxylation
Post Translational Protein Processing
Immunization
Collagen
Extremities
Amino Acids
Incidence

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Characterization of recombinant type II collagen : Arthritogenicity and tolerogenicity in DBA/1 mice. / Myers, Linda; Brand, David; Ye, X. J.; Cremer, M. A.; Rosloniec, E. F.; Bodo, M.; Myllyharju, J.; Helaakoski, T.; Nokelainen, M.; Pihlajaniemi, T.; Kivirikko, K.; Yang, C. L.; Alakokko, L.; Prockop, D. J.; Notbohm, H.; Fietzek, P.; Stuart, John; Kang, Andrew.

In: Immunology, Vol. 95, No. 4, 21.12.1998, p. 631-639.

Research output: Contribution to journalArticle

Myers, L, Brand, D, Ye, XJ, Cremer, MA, Rosloniec, EF, Bodo, M, Myllyharju, J, Helaakoski, T, Nokelainen, M, Pihlajaniemi, T, Kivirikko, K, Yang, CL, Alakokko, L, Prockop, DJ, Notbohm, H, Fietzek, P, Stuart, J & Kang, A 1998, 'Characterization of recombinant type II collagen: Arthritogenicity and tolerogenicity in DBA/1 mice', Immunology, vol. 95, no. 4, pp. 631-639. https://doi.org/10.1046/j.1365-2567.1998.00637.x
Myers, Linda ; Brand, David ; Ye, X. J. ; Cremer, M. A. ; Rosloniec, E. F. ; Bodo, M. ; Myllyharju, J. ; Helaakoski, T. ; Nokelainen, M. ; Pihlajaniemi, T. ; Kivirikko, K. ; Yang, C. L. ; Alakokko, L. ; Prockop, D. J. ; Notbohm, H. ; Fietzek, P. ; Stuart, John ; Kang, Andrew. / Characterization of recombinant type II collagen : Arthritogenicity and tolerogenicity in DBA/1 mice. In: Immunology. 1998 ; Vol. 95, No. 4. pp. 631-639.
@article{7d07172c346d4e66848486b7201c5402,
title = "Characterization of recombinant type II collagen: Arthritogenicity and tolerogenicity in DBA/1 mice",
abstract = "Recombinant human type II collagen (rhCII) was produced using both the HT1080 mammalian cell expression system (rhCII(ht)) and a baculovirus expression system (rhCII(bac)). The biosynthesis of CII requires extensive post-translational modifications, such as the hydroxylation of prolyl and lysyl residues and glycosylation of hydroxylysyl residues. Amino acid analyses indicated that the rhCII(bac) was adequately hydroxylated at prolyl residues but underhydroxylated at lysyl residues and underglycosylated compared with tissue-derived hCII, while rhCII(ht) was hyperhydroxylated and hyperglycosylated at lysyl residues. When the murine collagen-induced arthritis (CIA) model was used to investigate the immunological properties of the two forms of recombinant CII, each induced a high incidence of arthritis following immunization of susceptible mice when emulsified with complete Freund's adjuvant (CFA). However, the severity of the arthritis, as assessed by the number of affected limbs, was significantly higher in mice immunized with rhCII(ht) than in mice immunized with rhCII(bac). These data indicate that the degree of hydroxylysine glycosylation may play a role in the induction of the arthritogenic response to CII. Each of the recombinant collagens was comparable to tissue-derived hCII in their ability to induce tolerance and suppress arthritis when given as intravenous or oral tolerogens. Taken together, our data suggest that recombinant CII can be prepared in adequate amounts for therapeutic uses and that the material is immunologically comparable to tissue-derived hCII when used to induce tolerance.",
author = "Linda Myers and David Brand and Ye, {X. J.} and Cremer, {M. A.} and Rosloniec, {E. F.} and M. Bodo and J. Myllyharju and T. Helaakoski and M. Nokelainen and T. Pihlajaniemi and K. Kivirikko and Yang, {C. L.} and L. Alakokko and Prockop, {D. J.} and H. Notbohm and P. Fietzek and John Stuart and Andrew Kang",
year = "1998",
month = "12",
day = "21",
doi = "10.1046/j.1365-2567.1998.00637.x",
language = "English (US)",
volume = "95",
pages = "631--639",
journal = "Immunology",
issn = "0019-2805",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Characterization of recombinant type II collagen

T2 - Arthritogenicity and tolerogenicity in DBA/1 mice

AU - Myers, Linda

AU - Brand, David

AU - Ye, X. J.

AU - Cremer, M. A.

AU - Rosloniec, E. F.

AU - Bodo, M.

AU - Myllyharju, J.

AU - Helaakoski, T.

AU - Nokelainen, M.

AU - Pihlajaniemi, T.

AU - Kivirikko, K.

AU - Yang, C. L.

AU - Alakokko, L.

AU - Prockop, D. J.

AU - Notbohm, H.

AU - Fietzek, P.

AU - Stuart, John

AU - Kang, Andrew

PY - 1998/12/21

Y1 - 1998/12/21

N2 - Recombinant human type II collagen (rhCII) was produced using both the HT1080 mammalian cell expression system (rhCII(ht)) and a baculovirus expression system (rhCII(bac)). The biosynthesis of CII requires extensive post-translational modifications, such as the hydroxylation of prolyl and lysyl residues and glycosylation of hydroxylysyl residues. Amino acid analyses indicated that the rhCII(bac) was adequately hydroxylated at prolyl residues but underhydroxylated at lysyl residues and underglycosylated compared with tissue-derived hCII, while rhCII(ht) was hyperhydroxylated and hyperglycosylated at lysyl residues. When the murine collagen-induced arthritis (CIA) model was used to investigate the immunological properties of the two forms of recombinant CII, each induced a high incidence of arthritis following immunization of susceptible mice when emulsified with complete Freund's adjuvant (CFA). However, the severity of the arthritis, as assessed by the number of affected limbs, was significantly higher in mice immunized with rhCII(ht) than in mice immunized with rhCII(bac). These data indicate that the degree of hydroxylysine glycosylation may play a role in the induction of the arthritogenic response to CII. Each of the recombinant collagens was comparable to tissue-derived hCII in their ability to induce tolerance and suppress arthritis when given as intravenous or oral tolerogens. Taken together, our data suggest that recombinant CII can be prepared in adequate amounts for therapeutic uses and that the material is immunologically comparable to tissue-derived hCII when used to induce tolerance.

AB - Recombinant human type II collagen (rhCII) was produced using both the HT1080 mammalian cell expression system (rhCII(ht)) and a baculovirus expression system (rhCII(bac)). The biosynthesis of CII requires extensive post-translational modifications, such as the hydroxylation of prolyl and lysyl residues and glycosylation of hydroxylysyl residues. Amino acid analyses indicated that the rhCII(bac) was adequately hydroxylated at prolyl residues but underhydroxylated at lysyl residues and underglycosylated compared with tissue-derived hCII, while rhCII(ht) was hyperhydroxylated and hyperglycosylated at lysyl residues. When the murine collagen-induced arthritis (CIA) model was used to investigate the immunological properties of the two forms of recombinant CII, each induced a high incidence of arthritis following immunization of susceptible mice when emulsified with complete Freund's adjuvant (CFA). However, the severity of the arthritis, as assessed by the number of affected limbs, was significantly higher in mice immunized with rhCII(ht) than in mice immunized with rhCII(bac). These data indicate that the degree of hydroxylysine glycosylation may play a role in the induction of the arthritogenic response to CII. Each of the recombinant collagens was comparable to tissue-derived hCII in their ability to induce tolerance and suppress arthritis when given as intravenous or oral tolerogens. Taken together, our data suggest that recombinant CII can be prepared in adequate amounts for therapeutic uses and that the material is immunologically comparable to tissue-derived hCII when used to induce tolerance.

UR - http://www.scopus.com/inward/record.url?scp=15444348180&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=15444348180&partnerID=8YFLogxK

U2 - 10.1046/j.1365-2567.1998.00637.x

DO - 10.1046/j.1365-2567.1998.00637.x

M3 - Article

VL - 95

SP - 631

EP - 639

JO - Immunology

JF - Immunology

SN - 0019-2805

IS - 4

ER -