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 alpha ₂ 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 beta 1 (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 beta 1 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).