The effects of human macrophage inflammatory protein-1 alpha and its genetically modified variant, BB10010, on phagocyte function
| Autor: | S L, Williams, I E, Addison, E, Mollapour, L G, Czaplewski, D C, Linch, P J, Roberts |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Intracellular Fluid
Phagocytes Neutrophils Tumor Necrosis Factor-alpha Genetic Variation Granulocyte-Macrophage Colony-Stimulating Factor NADPH Oxidases In Vitro Techniques Macrophage Inflammatory Proteins Monocytes Recombinant Proteins Cell Line Humans Calcium Chemokine CCL4 Cell Adhesion Molecules Chemokine CCL3 Respiratory Burst |
| Zdroj: | Cytokines, cellularmolecular therapy. 3(1) |
| ISSN: | 1368-4736 |
| Popis: | BB-10010 is a genetically modified form of human macrophage inflammatory protein-1 alpha (MIP-1 alpha) 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-1 alpha and BB-10010 had identical dose-response curves in assays of calcium mobilization; however, neutrophils were less sensitive than monocytes to either MIP-1 alpha form, suggesting differences in receptor expression. Neither MIP-1 alpha type directly stimulated phagocyte superoxide production, nor did it have any priming effect on agonist-induced superoxide production. Both MIP-1 alpha and BB-10010 enhanced monocyte migration; however, cells were more 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-alpha 4) cell adhesion molecule expression was not seen with either MIP-1 alpha 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 proinflammatory effects on neutrophil activation, and this bodes well for its clinical use. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|