|Chemotaxis Induced by MSP and Neutralization by Human MSP Antibody. Recombinant Human MSP (Catalog # 352‑MS) chemoattracts mouse peritoneal resident macrophages in a dose-dependent manner (orange line). The amount of cells that migrated through the filter was measured by LeukoStat™ staining (Fisher Scientific). Chemotaxis elicited by Recombinant Human MSP (50 ng/mL) is neutralized (green line) by increasing concentrations of Goat Anti-Human MSP Antigen Affinity-purified Polyclonal Antibody (Catalog # AF352). The ND50 is typically 0.05‑0.2 µg/mL.|
Macrophage stimulating protein (MSP), also known as HGF-like protein, and scatter factor-2, is a member of the HGF family of growth factors (1). MSP is secreted as an inactive single chain precursor (pro-MSP) that contains a PAN/APPLE-like domain, four kringle domains, and a peptidase S1 domain which lacks enzymatic activity (2). Human MSP shares 79% aa sequence identity with mouse MSP and 44% aa sequence identity with human HGF. Pro-MSP is secreted by hepatocytes under the positive and negative control of CBP in complex with either HNF-4 or RAR, respectively (3). Circulating pro-MSP is proteolytically cleaved in response to tissue injury to yield biologically active disulfide linked heterodimers consisting of a 45‑62 kDa alpha and a 25‑35 kDa beta chain (4, 5). Pro-MSP can be activated by MT-SP1, a transmembrane protease that is expressed on macrophages and is upregulated in many cancers (6). Heterodimeric MSP as well as the isolated beta chain bind to MSP R/Ron with high-affinity, although only heterodimeric MSP can induce receptor dimerization and signaling (7, 8). MSP induces macrophage and keratinocyte proliferation and osteoclast activation (9, 10). It also inhibits LPS- or IFN-induced iNOS and IL-12 expression by macrophages and prevents apoptosis of epithelial cells separated from the ECM (11, 12).
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