The effects of human macrophage inflammatory protein-1α and its genetically modified variant, BB10010, on phagocyte function

Sion Llewelyn Williams, Ian E. Addison, Elahe Mollapour, Lloyd G. Czaplewski, David C. Linch, Pamela J. Roberts

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

BB-10010 is a genetically modified form of human macrophage inflammatory protein-1α (MIP-1α) with a single amino acid substitution of Asp26 by alanine, which inhibits aggregation of the native molecule. BB-10010 has stem cell protective properties, and has entered clinical trials for this purpose. The aim of this study was to determine the effects of BB-10010 on human phagocyte function and compare them with the native molecule. MIP-1α and BB-10010 had identical dose-response curves in assays of calcium mobilization; however, neutrophils were less sensitive than monocytes to either MIP-1α form, suggesting differences in receptor expression. Neither MIP-1α type directly stimulated phagocyte superoxide production, nor did it have any priming effect on agonist-induced superoxide production. Both MIP-1α and BB-10010 enhanced monocyte migration; however, cells were sensitive to the native molecule, with optimal effects seen at 1 ng/ml compared with 100 ng/ml BB-10010. Concomitant alteration of CD11b, CD18, and CD49d (VLA-α4) cell adhesion molecule expression was not seen with either MIP-1α type. With the exception of the difference in monocyte sensitivity in chemotaxis assays, BB-10010 reproduces the effects of the native molecule on phagocytes. BB-10010 does not have pro-inflammatory effects on neutrophil activation, and this bodes well for its clinical use.

Original languageEnglish (US)
Pages (from-to)41-50
Number of pages10
JournalCytokines, Cellular and Molecular Therapy
Volume3
Issue number1
StatePublished - Mar 1 1997
Externally publishedYes

Fingerprint

Chemokine CCL3
Macrophage Inflammatory Proteins
Phagocytes
Monocytes
Superoxides
Integrin alpha4beta1
Neutrophil Activation
Cell Adhesion Molecules
Chemotaxis
Amino Acid Substitution
Alanine
Neutrophils
Stem Cells
Clinical Trials
Calcium

Keywords

  • Calcium mobilization
  • Cell adhesion molecules
  • Chemokines
  • Chemotaxis
  • NADPH oxidase

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

The effects of human macrophage inflammatory protein-1α and its genetically modified variant, BB10010, on phagocyte function. / Williams, Sion Llewelyn; Addison, Ian E.; Mollapour, Elahe; Czaplewski, Lloyd G.; Linch, David C.; Roberts, Pamela J.

In: Cytokines, Cellular and Molecular Therapy, Vol. 3, No. 1, 01.03.1997, p. 41-50.

Research output: Contribution to journalArticle

Williams, Sion Llewelyn ; Addison, Ian E. ; Mollapour, Elahe ; Czaplewski, Lloyd G. ; Linch, David C. ; Roberts, Pamela J. / The effects of human macrophage inflammatory protein-1α and its genetically modified variant, BB10010, on phagocyte function. In: Cytokines, Cellular and Molecular Therapy. 1997 ; Vol. 3, No. 1. pp. 41-50.
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