Logo of jexpmedHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Exp Med. 1988 Feb 1; 167(2): 570–581.
PMCID: PMC2188834

Macrophages secrete a novel heparin-binding protein with inflammatory and neutrophil chemokinetic properties

Abstract

We report the identification and purification of a new inflammatory monokine synthesized by the macrophage tumor cell line RAW 264.7 in response to endotoxin. This monokine, which we term "macrophage inflammatory protein" (MIP), is a doublet with an apparent molecular mass of approximately 8,000 daltons on SDS-PAGE but forms aggregates of greater than 2 x 10(6) daltons as assessed by gel filtration. Partial NH2-terminal amino acid sequence data reveal no significant homology with any previously described protein. Although the monokine is anionic under physiological conditions, it is one of two major macrophage- secreted proteins that bind to heparin at high salt concentrations. At 100 ng/ml or greater, MIP is chemokinetic for human polymorphonuclear cells and triggers hydrogen peroxide production. Subcutaneous injection of 10 ng or greater of MIP into footpads of C3H/HeJ mice elicits an inflammatory response, characterized by neutrophil infiltration. These findings suggest that MIP is an endogenous mediator that may play a role in the host responses that occur during endotoxemia and other inflammatory events.

Full Text

The Full Text of this article is available as a PDF (856K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Nathan CF. Secretory products of macrophages. J Clin Invest. 1987 Feb;79(2):319–326. [PMC free article] [PubMed]
  • Beutler B, Cerami A. Cachectin and tumour necrosis factor as two sides of the same biological coin. Nature. 1986 Apr 17;320(6063):584–588. [PubMed]
  • Dinarello CA. An update on human interleukin-1: from molecular biology to clinical relevance. J Clin Immunol. 1985 Sep;5(5):287–297. [PubMed]
  • Dinarello CA. Interleukin-1. Rev Infect Dis. 1984 Jan-Feb;6(1):51–95. [PubMed]
  • Kampschmidt RF. The numerous postulated biological manifestations of interleukin-1. J Leukoc Biol. 1984 Sep;36(3):341–355. [PubMed]
  • Georgilis K, Schaefer C, Dinarello CA, Klempner MS. Human recombinant interleukin 1 beta has no effect on intracellular calcium or on functional responses of human neutrophils. J Immunol. 1987 May 15;138(10):3403–3407. [PubMed]
  • Yoshimura T, Matsushima K, Oppenheim JJ, Leonard EJ. Neutrophil chemotactic factor produced by lipopolysaccharide (LPS)-stimulated human blood mononuclear leukocytes: partial characterization and separation from interleukin 1 (IL 1). J Immunol. 1987 Aug 1;139(3):788–793. [PubMed]
  • Beutler B, Mahoney J, Le Trang N, Pekala P, Cerami A. Purification of cachectin, a lipoprotein lipase-suppressing hormone secreted by endotoxin-induced RAW 264.7 cells. J Exp Med. 1985 May 1;161(5):984–995. [PMC free article] [PubMed]
  • Sassa S, Wolpe S, Cerami A. Inhibition of erythroid differentiation of mouse erythroleukemia cells by a macrophage product(s). Blood Cells. 1987;13(1-2):161–169. [PubMed]
  • Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. [PubMed]
  • Granstein RD, Margolis R, Mizel SB, Sauder DN. In vivo inflammatory activity of epidermal cell-derived thymocyte activating factor and recombinant interleukin 1 in the mouse. J Clin Invest. 1986 Mar;77(3):1020–1027. [PMC free article] [PubMed]
  • Klempner MS, Dinarello CA, Henderson WR, Gallin JI. Stimulation of neutrophil oxygen-dependent metabolism by human leukocytic pyrogen. J Clin Invest. 1979 Oct;64(4):996–1002. [PMC free article] [PubMed]
  • BOYDEN S. The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leucocytes. J Exp Med. 1962 Mar 1;115:453–466. [PMC free article] [PubMed]
  • Hesse DG, Cole DJ, Van Epps DE, Williams RC., Jr Decreased T lymphocyte migration in patients with malignancy mediated by a suppressor cell population. J Clin Invest. 1984 Apr;73(4):1078–1085. [PMC free article] [PubMed]
  • Nathan CF. Neutrophil activation on biological surfaces. Massive secretion of hydrogen peroxide in response to products of macrophages and lymphocytes. J Clin Invest. 1987 Dec;80(6):1550–1560. [PMC free article] [PubMed]
  • De la Harpe J, Nathan CF. A semi-automated micro-assay for H2O2 release by human blood monocytes and mouse peritoneal macrophages. J Immunol Methods. 1985 Apr 22;78(2):323–336. [PubMed]
  • Moldawer LL, Lonnroth C, Mizel SB, Lundholm KG. Down-regulation of interleukin 1 production by macrophages of sarcoma-bearing mice. J Immunol. 1987 Jun 15;138(12):4270–4274. [PubMed]
  • Ostrove JM, Gifford GE. Stimulation of RNA synthesis in L-929 cells by rabbit tumor necrosis factor. Proc Soc Exp Biol Med. 1979 Mar;160(3):354–358. [PubMed]
  • Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. [PubMed]
  • Figari IS, Mori NA, Palladino MA., Jr Regulation of neutrophil migration and superoxide production by recombinant tumor necrosis factors-alpha and -beta: comparison to recombinant interferon-gamma and interleukin-1 alpha. Blood. 1987 Oct;70(4):979–984. [PubMed]
  • Ming WJ, Bersani L, Mantovani A. Tumor necrosis factor is chemotactic for monocytes and polymorphonuclear leukocytes. J Immunol. 1987 Mar 1;138(5):1469–1474. [PubMed]
  • Shalaby MR, Aggarwal BB, Rinderknecht E, Svedersky LP, Finkle BS, Palladino MA., Jr Activation of human polymorphonuclear neutrophil functions by interferon-gamma and tumor necrosis factors. J Immunol. 1985 Sep;135(3):2069–2073. [PubMed]
  • Klebanoff SJ, Vadas MA, Harlan JM, Sparks LH, Gamble JR, Agosti JM, Waltersdorph AM. Stimulation of neutrophils by tumor necrosis factor. J Immunol. 1986 Jun 1;136(11):4220–4225. [PubMed]
  • Tsujimoto M, Yokota S, Vilcek J, Weissmann G. Tumor necrosis factor provokes superoxide anion generation from neutrophils. Biochem Biophys Res Commun. 1986 Jun 30;137(3):1094–1100. [PubMed]

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

Formats:

Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem chemical compound records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records. Multiple substance records may contribute to the PubChem compound record.
  • Gene
    Gene
    Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
  • GEO Profiles
    GEO Profiles
    Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
  • HomoloGene
    HomoloGene
    HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.
  • MedGen
    MedGen
    Related information in MedGen
  • OMIM
    OMIM
    Genome Survey Sequence (GSS) nucleotide records reported in the current articles.
  • Protein
    Protein
    Protein translation features of primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...