Logo of jexpmedHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Exp Med. May 1, 1996; 183(5): 2379–2384.
PMCID: PMC2192560

Monocyte chemotactic protein 4 (MCP-4), a novel structural and functional analogue of MCP-3 and eotaxin

Abstract

A novel human CC chemokine complementary DNA was identified in a library constructed from human fetal RNA, cloned into a baculovirus vector, and expressed in Sf9 insect cells. The mature recombinant protein that was released had the NH2-terminal sequence pyro- QPDALNVPSTC...and consisted of 75 amino acids. Minor amounts of two variants of 77 and 82 residues (NH2 termini: LAQPDA...and FNPQGLAQPDA...) were released as well. The novel chemokine was designated monocyte chemotactic protein 4 (MCP-4) and the variants were designated (LA)MCP-4 and (FNPQGLA)MCP-4. MCP-4 shares the pyroglutamic acidproline NH2-terminal motif and 56-61% sequence identity with the three known monocyte chemotactic proteins and is 60% identical to eotaxin. It has marked functional similarities to MCP-3 and eotaxin. Like MCP-3, MCP-4 is a chemoattractant of high efficacy for monocytes and T lymphocytes. On these cells, it binds to receptors that recognize MCP-1, MCP-3, and RANTES. On eosinophils, MCP-4 has similar efficacy and potency as MCP-3, RANTES, and cotaxin. It shares receptors with eotaxin and shows full cross-desensitization with this cosinophil- selective chemokine. Of the two variants, only (LA)MCP-4 could be purified in sufficient quantities for testing and was found to be at least 30-fold less potent than MCP-4 itself. This suggests that the 75- residue form with the characteristic NH2 terminus of an MCP is the biologically relevant species.

Full Text

The Full Text of this article is available as a PDF (534K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Baggiolini M, Dewald B, Moser B. Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines. Adv Immunol. 1994;55:97–179. [PubMed]
  • Yoshimura T, Robinson EA, Tanaka S, Appella E, Kuratsu J, Leonard EJ. Purification and amino acid analysis of two human glioma-derived monocyte chemoattractants. J Exp Med. 1989 Apr 1;169(4):1449–1459. [PMC free article] [PubMed]
  • Van Damme J, Proost P, Lenaerts JP, Opdenakker G. Structural and functional identification of two human, tumor-derived monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine family. J Exp Med. 1992 Jul 1;176(1):59–65. [PMC free article] [PubMed]
  • Uguccioni M, D'Apuzzo M, Loetscher M, Dewald B, Baggiolini M. Actions of the chemotactic cytokines MCP-1, MCP-2, MCP-3, RANTES, MIP-1 alpha and MIP-1 beta on human monocytes. Eur J Immunol. 1995 Jan;25(1):64–68. [PubMed]
  • Loetscher P, Seitz M, Clark-Lewis I, Baggiolini M, Moser B. Monocyte chemotactic proteins MCP-1, MCP-2, and MCP-3 are major attractants for human CD4+ and CD8+ T lymphocytes. FASEB J. 1994 Oct;8(13):1055–1060. [PubMed]
  • Carr MW, Roth SJ, Luther E, Rose SS, Springer TA. Monocyte chemoattractant protein 1 acts as a T-lymphocyte chemoattractant. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3652–3656. [PMC free article] [PubMed]
  • Kuna P, Reddigari SR, Rucinski D, Oppenheim JJ, Kaplan AP. Monocyte chemotactic and activating factor is a potent histamine-releasing factor for human basophils. J Exp Med. 1992 Feb 1;175(2):489–493. [PMC free article] [PubMed]
  • Alam R, Lett-Brown MA, Forsythe PA, Anderson-Walters DJ, Kenamore C, Kormos C, Grant JA. Monocyte chemotactic and activating factor is a potent histamine-releasing factor for basophils. J Clin Invest. 1992 Mar;89(3):723–728. [PMC free article] [PubMed]
  • Bischoff SC, Krieger M, Brunner T, Dahinden CA. Monocyte chemotactic protein 1 is a potent activator of human basophils. J Exp Med. 1992 May 1;175(5):1271–1275. [PMC free article] [PubMed]
  • Dahinden CA, Geiser T, Brunner T, von Tscharner V, Caput D, Ferrara P, Minty A, Baggiolini M. Monocyte chemotactic protein 3 is a most effective basophil- and eosinophil-activating chemokine. J Exp Med. 1994 Feb 1;179(2):751–756. [PMC free article] [PubMed]
  • Rot A, Krieger M, Brunner T, Bischoff SC, Schall TJ, Dahinden CA. RANTES and macrophage inflammatory protein 1 alpha induce the migration and activation of normal human eosinophil granulocytes. J Exp Med. 1992 Dec 1;176(6):1489–1495. [PMC free article] [PubMed]
  • Jose PJ, Griffiths-Johnson DA, Collins PD, Walsh DT, Moqbel R, Totty NF, Truong O, Hsuan JJ, Williams TJ. Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation. J Exp Med. 1994 Mar 1;179(3):881–887. [PMC free article] [PubMed]
  • Rothenberg ME, Luster AD, Leder P. Murine eotaxin: an eosinophil chemoattractant inducible in endothelial cells and in interleukin 4-induced tumor suppression. Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8960–8964. [PMC free article] [PubMed]
  • Ponath PD, Qin S, Ringler DJ, Clark-Lewis I, Wang J, Kassam N, Smith H, Shi X, Gonzalo JA, Newman W, et al. Cloning of the human eosinophil chemoattractant, eotaxin. Expression, receptor binding, and functional properties suggest a mechanism for the selective recruitment of eosinophils. J Clin Invest. 1996 Feb 1;97(3):604–612. [PMC free article] [PubMed]
  • Gentz R, Hayes A, Grau N, Fountoulakis M, Lahm HW, Ozmen L, Garotta G. Analysis of soluble human and mouse interferon-gamma receptors expressed in eukaryotic cells. Eur J Biochem. 1992 Dec 1;210(2):545–554. [PubMed]
  • Clark-Lewis I, Moser B, Walz A, Baggiolini M, Scott GJ, Aebersold R. Chemical synthesis, purification, and characterization of two inflammatory proteins, neutrophil activating peptide 1 (interleukin-8) and neutrophil activating peptide. Biochemistry. 1991 Mar 26;30(12):3128–3135. [PubMed]
  • Peveri P, Walz A, Dewald B, Baggiolini M. A novel neutrophil-activating factor produced by human mononuclear phagocytes. J Exp Med. 1988 May 1;167(5):1547–1559. [PMC free article] [PubMed]
  • von Tscharner V, Prod'hom B, Baggiolini M, Reuter H. Ion channels in human neutrophils activated by a rise in free cytosolic calcium concentration. Nature. 324(6095):369–372. [PubMed]
  • Padrines M, Wolf M, Walz A, Baggiolini M. Interleukin-8 processing by neutrophil elastase, cathepsin G and proteinase-3. FEBS Lett. 1994 Sep 26;352(2):231–235. [PubMed]
  • Gong JH, Clark-Lewis I. Antagonists of monocyte chemoattractant protein 1 identified by modification of functionally critical NH2-terminal residues. J Exp Med. 1995 Feb 1;181(2):631–640. [PMC free article] [PubMed]
  • Weber M, Uguccioni M, Ochensberger B, Baggiolini M, Clark-Lewis I, Dahinden CA. Monocyte chemotactic protein MCP-2 activates human basophil and eosinophil leukocytes similar to MCP-3. J Immunol. 1995 Apr 15;154(8):4166–4172. [PubMed]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...