rfeFlt-3 Ligand/FL (25 ug)

Background: Flt-3 Ligand/FLT3L

Flt-3 Ligand, also known as FLT3L, is an alpha-helical cytokine that promotes the differentiation of multiple hematopoietic cell lineages (1-3). Mature feline Flt-3 Ligand consists of a 156 amino acid (aa) extracellular region with a cytokine-like domain and a juxtamembrane tether region, a 21 aa transmembrane segment, and an 88 aa cytoplasmic tail (4, 5). Within the ECD, feline Flt-3 Ligand shares 92%, 81%, 70%, and 63% aa sequence identity with canine, human, mouse, and rat Flt-3 Ligand, respectively. Flt-3 Ligand is expressed as a noncovalently-linked dimer by T cells and bone marrow and thymic fibroblasts (1, 6). Each 36 kDa chain of the Flt-3 Ligand dimer carries approximately 12 kDa of N- and O-linked carbohydrates (6). Alternate splicing and proteolytic cleavage of the transmembrane form of the Flt-3 Ligand protein can generate a soluble 30 kDa fragment that includes the cytokine-like domain (6, 7). Multiple splice forms of canine, human, and mouse Flt-3 Ligand have been described and may also exist in feline (4, 6-10). Both transmembrane and soluble Flt-3 Ligand signal through the tyrosine kinase receptor Flt-3/Flk-2 (3, 5, 7, 10). Flt-3 Ligand induces the expansion of monocytes and immature dendritic cells as well as early B cell lineage differentiation (2, 11). Additionally, Flt-3 Ligand synergizes with IL-3, GM-CSF, and SCF to promote the mobilization and myeloid differentiation of hematopoietic stem cells (7, 8, 10). Flt-3 Ligand also cooperates with IL-2, IL-6, IL-7, and -15 to induce NK cell development and with IL-3, IL-7, and IL-11 to induce terminal B cell maturation (1, 12). Animal studies also show Flt-3 Ligand reduces the severity of experimentally induced allergic inflammation (13).