Recombinant Mouse SIRP alpha/CD172a Fc Chimera Protein, CF

Signal regulatory protein alpha (SIRP alpha, designated CD172a), also called SHPS-1 (SHP substrate 1) and previously, MyD-1 (Myeloid/Dendritic-1), is a homodimeric, 100-105 kDa type I transmembrane glycoprotein that belongs to the SIRP/SHPS (CD172) family of the immunoglobulin superfamily (1-5). SIRPs are paired receptors, with similar extracellular domains but differing C-termini and functions (1, 2). The 513 amino acid (aa) mouse SIRP alpha contains a 342 aa extracellular domain (ECD) with one V‑type and two C1 type Ig domains and many potential N‑glycosylation sites. It has a 117 aa cytoplasmic sequence with ITIM motifs that recruit tyrosine phosphatases SHP-1 and SHP-2 when phosphorylated (4). Mouse and human SIRP alpha have at least 30 described polymorphisms, including the human SIRP alpha prominent variant BIT (Brain Ig like molecule with Tyrosine-based activation motifs, also called SIRP alpha₂ or PTPNS) (2). In mouse, one splice variant lacks aa 147-364, which eliminates the C type Ig domains, while another lacks only aa 425-428 (6). Mouse SIRP alpha ECD shares 61%, 75%, 62%, 61%, and 59% aa sequence identity with human, rat, equine, bovine, and porcine SIRP alpha, respectively, and shares 62% aa identity with mouse SIRP beta1 (2). SIRP alpha is expressed mainly on myeloid cells, including macrophages, neutrophils, dendritic and Langerhans cells (3 ‑ 7). It is also found on neurons, smooth muscle and endothelial cells (8-10). SIRP alpha shows adhesion to the ubiquitous CD47/IAP (integrin associated protein), while SIRP gamma binds more weakly and SIRP beta1 does not bind at all (1, 2). Mouse and human SIRP alpha are allelic in nature, and variation(s) in the V-type Ig-like domain likely impacts its binding to CD47 (11). SIRP alpha engagement generally produces a negative regulatory signal (4). Low SIRP alpha recognition of CD47, which occurs on aged erythrocytes or platelets or xenogenic cells, promotes clearance of CD47^low cells from circulation (12 ‑ 14). SIRP alpha recognition of surfactants SP‑A and SP‑D in the lung can inhibit alveolar macrophage cytokine production (15). The CD47 integrin-SIRP alpha interaction is reported to promote macrophage fusion during osteoclastogenesis (16).