Levels of L‐Selectin (CD62L) on Human Leukocytes in Disseminated Cryptococcosis With and Without Associated HIV‐1 Infection

Abstract

Patients with disseminated cryptococcosis typically have measurable levels of cryptococcal polysaccharide in serum samples but minimal leukocyte infiltration into infected tissues. In vitro data have shown that cryptococcal polysaccharide induces L-selectin (CD62L) shedding from leukocytes. To assess shedding in vivo, we compared leukocyte L-selectin levels in human immunodeficiency virus (HIV) type 1-negative and -positive subjects with and without circulating cryptococcal polysaccharide. Results showed that subjects with cryptococcal polysaccharide in serum samples have significantly lower percentages of neutrophils, monocytes, and CD3+ T cells with L-selectin on their surfaces than do healthy subjects, regardless of HIV status. There was significantly more soluble L-selectin in serum samples from subjects with cryptococcosis than in those from uninfected subjects. Reduced L-selectin levels on leukocytes in subjects with circulating cryptococcal polysaccharide and increased serum levels of soluble L-selectin indicates that surface L-selectin shedding is a mechanism that likely explains reduced leukocyte extravasation into infected tissues of patients with disseminated cryptococcosis.

The Neutrophil

“…GXM also induces shedding of the TNF receptor, TNFR p75-80 (Dong and Murphy, 1996), and interferes with E-selectin-mediated binding of neutrophils to endothelial cells (Ellerbroek et al, 2004), in a CD14/TLR4-dependent fashion. In keeping with these in vitro results, individuals with systemic cryptococcal infection and detectable serum levels of cryptococcal polysaccharide have decreased levels of L-selectin in peripheral blood neutrophils and increased levels of soluble Lselectin in serum (Jackson et al, 2005). GXM also binds to a principal neutrophil integrin, CD18, and may inhibit the interaction of 2 integrins with their ligand ICAM-1 (Dong and Murphy, 1997).…”

Subcellular localization of L-selectin ligand in the endometrium implies a novel function for pinopodes in endometrial receptivity

“…More interestingly, a significant difference between the expression of L-selectin ligands between fertile and infertile women was reported and the MECA-79 epitopes were shown to be expressed at a higher level in fertile compared to that of infertile patients [14,15]. Other than embryo implantation [10,16], this adhesion system correlates with many physiological and pathological processes including leukocyte infiltration [17,18], lymphocyte homing [19], and tumor metastasis [20,21] indicating the existence of similar pathways between these processes. Since the apical surface of the endometrium contains key elements for the initiation of molecular interactions between human blastocysts and the endometrium, and that the L-selectin ligand adhesion system is believed to play a major role in mediating initial embryonic apposition and adhesion, this prompted us to investigate the subcellular localization of L-selectin ligand at the pinopodes, the most apical surfaces of the receptive endometrium [22], and the first embryo-maternal contact sites.…”

Association between soluble L-selectin and anti-JCV antibodies in natalizumab-treated relapsing-remitting MS patients

“…Moreover, in the recent study of these authors, the positive correlation between cellular Lselectin expression on T cells and anti-JCV antibody index values in natalizumab-treated patients was detected (Schwab et al, 2014). Interestingly, low cell-surface L-selectin levels have been shown to be associated with increased serum levels of sL-selectin that is due to shedding of L-selectin from the cell surface, a mechanism possibly explaining reduced leukocyte extravasation into tissues (Jackson et al, 2005). These observations are in line with our result of increased level of sL-selectin indicative of increased PML risk in natalizumab-treated patients.…”