Surfactant protein D (Sp-D) binds to membrane-proximal domain (D3) of signal regulatory protein α (SIRPα), a site distant from binding domain of CD47, while also binding to analogous region on signal regulatory protein ß (SIRPß).

Signal regulatory protein α (SIRPα), a highly glycosylated type-1 transmembrane protein, is composed of three immunoglobulin-like extracellular loops as well as a cytoplasmic tail containing three classical tyrosine-based inhibitory motifs. Previous reports indicate that SIRPα binds to humoral pattern recognition molecules in the collectin family, namely surfactant proteins D and A (Sp-D and Sp-A, respectively), which are heavily expressed in the lung and constitute one of the first lines of innate immune defense against pathogens. However, little is known about molecular details of the structural interaction of Sp-D with SIRPs. In the present work, we examined the molecular basis of Sp-D binding to SIRPα using domain-deleted mutant proteins. We report that Sp-D binds to the membrane-proximal Ig domain (D3) of SIRPα in a calcium- and carbohydrate-dependent manner. Mutation of predicted N-glycosylation sites on SIRPα indicates that Sp-D binding is dependent on interactions with specific N-glycosylated residues on the membrane-proximal D3 domain of SIRPα. Given the remarkable sequence similarity of SIRPα to SIRPß and the lack of known ligands for the latter, we examined Sp-D binding to SIRPß. Here, we report specific binding of Sp-D to the membrane-proximal D3 domain of SIRPß. Further studies confirmed that Sp-D binds to SIRPα expressed on human neutrophils and differentiated neutrophil-like cells. Because the other known ligand of SIRPα, CD47, binds to the membrane-distal domain D1, these findings indicate that multiple, distinct, functional ligand binding sites are present on SIRPα that may afford differential regulation of receptor function.

Comparison of success rate and intraocular pressure spikes between selective laser trabeculoplasty and micropulse laser trabeculoplasty in African American and Hispanic patients.

AIM: To examine the efficacy and safety of micropulse laser trabeculoplasty (MLT) versus selective laser trabeculoplasty (SLT) in a large cohort of primarily African American and Hispanic patients. METHODS: A single center retrospective comparative cohort review conducted at Cook County Health facilities that included patients with a diagnosis of open angle glaucoma or ocular hypertension who received an SLT or MLT procedure between January 2017 and May 2021. RESULTS: Totally 131 eyes of 99 patients were analyzed. The 77 eyes received SLT and 54 received MLT. Seven out of 77 eyes in the SLT group (9.1%) and 1 out of 54 eyes in the MLT group (1.9%) had an IOP spike (defined as > 5 mm Hg) at either 1h or 1wk after procedure (P=0.05, Chi-squared test with Haldane-Anscombe correction). The procedure failure rate at one year was 50% for SLT and 48% for MLT (P=0.31). CONCLUSION: MLT has a significantly lower incidence of pressure spikes and a similar treatment failure rate at 1-year post-procedure, demonstrating that it is a reasonable alternative compared to SLT.