Ly6 family proteins in neutrophil biology

Lee, Pui Y.; Wang, Junxia; Parisini, Emilio; Dascher, Christopher C.; Nigrović, Peter A.

doi:10.1189/jlb.0113014

Cited by 255 publications

(259 citation statements)

References 99 publications

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“…From a functional point of view, this protein fold has proven highly versatile, as evolution has created single domain paralogs with such diverse functions as bona fide cytotoxins that inhibit acetylcholine esterases (fasciculins), ion channels (calciseptine) or nicotinic acetylcholine receptors (e.g., α-neurotoxins), inhibitors of autologous complement activation (CD59), cofactors of lipolysis enabling trans-capillary trafficking of lipoprotein lipase (GPIHBP-1), and maintenance of paracellular diffusion barriers in Drosophila by trafficking and assembly of septate junction components (crooked, crimpled, coiled, and boudin) (Kini and Doley 2010;Nilton et al 2010;Nevo et al 2013;Young and Zechner 2013). Nevertheless, the biochemical function of a large proportion of these single domain LU-proteins still remains enigmatic, as illustrated by the >20 murine Ly-6 antigens encoded on chromosome 15 and predominantly expressed by neutrophils (Lee et al 2013). A specialized subgroup of the LU-protein family is encoded by a small gene cluster located on human chromosome 19, which comprises six multidomain membrane proteins (Supplemental Fig.…”

Section: Discussionmentioning

confidence: 99%

The Urokinase Receptor Homolog Haldisin Is a Novel Differentiation Marker of Stratum Granulosum in Squamous Epithelia

Gårdsvoll

Kriegbaum

Hertz

et al. 2013

J Histochem Cytochem.

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Several members of the Ly-6/uPAR (LU)-protein domain family are differentially expressed in human squamous epithelia. In some cases, they even play important roles in maintaining skin homeostasis, as exemplified by the secreted single domain member, SLURP-1, the deficiency of which is associated with the development of palmoplantar hyperkeratosis in the congenital skin disorder Mal de Meleda. In the present study, we have characterized a new member of the LU-protein domain family, which we find to be predominantly expressed in the stratum granulosum of human skin, thus resembling the expression of SLURP-1. In accordance with its expression pattern, we denote this protein product, which is encoded by the LYPD5 gene, as Haldisin (human antigen with LU-domains expressed in skin). Two of the five human glycolipid-anchored membrane proteins with multiple LU-domains characterized so far are predominantly confined to squamous epithelia (i.e., C4.4A), to stratum spinosum, and Haldisin to stratum granulosum under normal homeostatic conditions. Whether Haldisin is a prognostic biomarker for certain epithelial malignancies, like C4.4A and SLURP-1, remains to be explored.

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Section: Discussionmentioning

confidence: 99%

The Urokinase Receptor Homolog Haldisin Is a Novel Differentiation Marker of Stratum Granulosum in Squamous Epithelia

Gårdsvoll

Kriegbaum

Hertz

et al. 2013

J Histochem Cytochem.

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“…In mouse peripheral blood, Ly6G is expressed exclusively on granulocytes (11,18), and the density of Ly6G on circulating neutrophils is increased compared to Ly6G density on bone marrow segregated neutrophils (18). Ly6G is absent from basophils, while low to intermediate Ly6G density has been reported on eosinophils (18).…”

Section: Development Of Mouse Anc Assays Using Single Fcm Platformsmentioning

confidence: 99%

Absolute counting of neutrophils in whole blood using flow cytometry

et al. 2014

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Absolute neutrophil count (ANC) is used clinically to monitor physiological dysfunctions such as myelosuppression or infection. In the research laboratory, ANC is a valuable measure to monitor the evolution of a wide range of disease states in disease models. Flow cytometry (FCM) is a fast, widely used approach to confidently identify thousands of cells within minutes. FCM can be optimised for absolute counting using spiked-in beads or by measuring the sample volume analysed. Here we combine the 1A8 antibody, specific for the mouse granulocyte protein Ly6G, with flow cytometric counting in straightforward FCM assays for mouse ANC, easily implementable in the research laboratory. Volumetric and Trucount TM bead assays were optimized for mouse neutrophils, and ANC values obtained with these protocols were compared to ANC measured by a dual-platform assay using the Orphee Mythic 18 veterinary haematology analyser. The single platform assays were more precise with decreased intra-assay variability compared with ANC obtained using the dual protocol. Defining ANC based on Ly6G expression produces a 15% higher estimate than the dual protocol. Allowing for this difference in ANC definition, the flow cytometry counting assays using Ly6G can be used reliably in the research laboratory to quantify mouse ANC from a small volume of blood. We demonstrate the utility of the volumetric protocol in a time-course study of chemotherapy induced neutropenia using four drug regimens. V C 2014 International Society for Advancement of CytometryKey terms absolute count; neutrophils; ANC; flow cytometry; volumetry; single-platform; doubleplatform THE concentration of blood circulating neutrophils is considerably altered by a wide range of physical and chemical stimuli such as microbial infections, gamma irradiation, and chemotherapy. Fluctuations outside of the normal range of absolute neutrophil count (ANC) correlate with increased morbidity and mortality (1). ANC is a relevant clinical parameter (2) and is routinely obtained from automated haematology instruments. However, more than 25% of samples require additional manual review of peripheral blood smears, usually because measurements fall outside the acceptable range of the instrument (3). Manual smear inspection increases workload and cost while reducing ANC accuracy. Hence, standardized flow cytometry (FCM) absolute count protocols are being pursued for implementation in the clinic (4). Even in research laboratories where flow cytometers are prevalent, ANC is obtained with veterinary haematology analysers (5) and often outsourced (6). At the time of writing, there is no published protocol to measure mouse ANC using a single, straightforward, flow cytometric assay.FCM protocols are available for absolute counting of other white blood cell (WBC) subpopulations in animal experimental models and in humans (7). Volumetric FCM involves the systematic measurement of all volumes throughout the procedure, including the volume acquired on the flow cytometer. Therefore, with a simple

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“…Cellular populations were analyzed in whole-lung homogenate at 2, 24, and 48 h post-intranasal administration. Flow cytometric analysis was performed, and populations were identified with the following surface marker combinations: dendritic cells (CD11c + CD11b − ), interstitial macrophages (CD11c − CD11b + F4/80 + ), neutrophils (CD11b + Ly6G/C Gr-1 + ), and activated monocytes (CD11b + Ly6G/C Gr-1 − ) (44)(45)(46)(47). Figure 5 shows the cellular population distribution in the lungs.…”

Section: Distribution Of Lung Cellular Populationsmentioning

confidence: 99%

Safety and Biocompatibility of Carbohydrate-Functionalized Polyanhydride Nanoparticles

Vela-Ramirez

Goodman

Boggiatto

et al. 2014

AAPS J

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ABSTRACT. Carbohydrate functionalization of nanoparticles allows for targeting of C-type lectin receptors. This family of pattern recognition receptors expressed on innate immune cells, such as macrophages and dendritic cells, can be used to modulate immune responses. In this work, the in vivo safety profile of carbohydrate-functionalized polyanhydride nanoparticles was analyzed following parenteral and intranasal administration in mice. Polyanhydride nanoparticles based on 1,6-bis-(pcarboxyphenoxy)hexane and 1,8-bis-(p-carboxyphenoxy)-3,6-dioxaoctane were used. Nanoparticle functionalization with di-mannose (specifically carboxymethyl-α-D-mannopyranosyl-(1,2)-Dmannopyranoside), galactose (specifically carboxymethyl-β-galactoside), or glycolic acid induced no adverse effects after administration based on histopathological evaluation of liver, kidneys, and lungs. Regardless of the polymer formulation, there was no evidence of hepatic or renal damage or dysfunction observed in serum or urine samples. The histological profile of cellular infiltration and the cellular distribution and kinetics in the lungs of mice administered with nanoparticle treatments followed similar behavior as that observed in the lungs of animals administered with saline. Cytokine and chemokine profiles in bronchoalveolar lavage fluid indicated surface chemistry dependence on modest secretion of IL-6, IP-10, and MCP-1; however, there was no evidence of any deleterious histopathological changes. Based on these analyses, carbohydrate-functionalized nanoparticles are safe for in vivo applications. These results provide foundational information towards the evaluation of the capabilities of these surface-modified nanoparticles as vaccine delivery formulations.

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Ly6 family proteins in neutrophil biology

Cited by 255 publications

References 99 publications

The Urokinase Receptor Homolog Haldisin Is a Novel Differentiation Marker of Stratum Granulosum in Squamous Epithelia

The Urokinase Receptor Homolog Haldisin Is a Novel Differentiation Marker of Stratum Granulosum in Squamous Epithelia

Absolute counting of neutrophils in whole blood using flow cytometry

Safety and Biocompatibility of Carbohydrate-Functionalized Polyanhydride Nanoparticles

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