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 language | English (US) |
|---|---|
| Pages (from-to) | 41-50 |
| Number of pages | 10 |
| Journal | Cytokines, Cellular and Molecular Therapy |
| Volume | 3 |
| Issue number | 1 |
| State | Published - Mar 1 1997 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - The effects of human macrophage inflammatory protein-1α and its genetically modified variant, BB10010, on phagocyte function
AU - Williams, Sion Llewelyn
AU - Addison, Ian E.
AU - Mollapour, Elahe
AU - Czaplewski, Lloyd G.
AU - Linch, David C.
AU - Roberts, Pamela J.
PY - 1997/3/1
Y1 - 1997/3/1
N2 - 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.
AB - 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.
KW - Calcium mobilization
KW - Cell adhesion molecules
KW - Chemokines
KW - Chemotaxis
KW - NADPH oxidase
UR - http://www.scopus.com/inward/record.url?scp=0030752683&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030752683&partnerID=8YFLogxK
M3 - Article
C2 - 9287243
AN - SCOPUS:0030752683
VL - 3
SP - 41
EP - 50
JO - Cytokines, Cellular and Molecular Therapy
JF - Cytokines, Cellular and Molecular Therapy
SN - 1368-4736
IS - 1
ER -