Soluble L-selectin is present in human plasma at high levels and retains functional activity.

Abstract

Abstract. L-selectin expressed by granulocytes, lymphocytes, and monocytes is responsible for initial leukocyte attachment to inflamed endothelium and high endothelial venules of peripheral lymph nodes. After leukocyte activation in vitro, L-selectin is rapidly shed from the cell surface. In this study, shed L-selectin (sL-selectin) from both lymphocytes and neutrophils was demonstrated to be present in high levels in human plasma by Western blot analysis and using a quantitative ELISA. In serum from normal human blood donors, a mean sL-selectin level of 1.6 ___ 0.8 #g/ml (n = 63) was found by ELISA. In addition, semipurified sL-selectin from plasma inhibited L-selectinspecific attachment of lymphocytes to cytokineactivated endothelium in a dose-dependent manner. L-selectin-dependent leukocyte attachment was completely inhibited at sL-selectin concentrations of 8-15 /zg/ml, while physiological concentrations of sLselectin caused a small but consistent inhibition of lymphocyte attachment, sL-selectin in plasma also inhibited anti-L-selectin mAb (2-5 #g/ml) binding to the surface of leukocytes. Interestingly, one epitope present within the EGF-like domain of L-selectin was lost in sL-selectin, suggesting a conformational change in the structure of the receptor after shedding. The presence of serum sL-selectin with functional activity indicates a potential role for sL-selectin in the regulation of leukocyte attachment to endothelium.T HE ability of leukocytes to leave the circulation and to migrate into tissues is a critical feature of the immune response. Several adhesion molecules are involved in the process of adhesion and transmigration of leukocytes through vascular endothelium at sites of inflammation (45). One molecule responsible for the initial attachment of leukocytes to endothelium is L-selectin (Leukocyte Adhesion Molecule-1 [LAM-1] t MEL-14) (24,30,43,44). L-selectin is a member of the selectin family of adhesion molecules (3,11,27,36,37,49) that includes E-selectin (Endothelial-Leukocyte Adhesion Molecule-1 [ELAM-1]) (1, 2, 31, 32) and CD62 (P-selectin, PADGEM, GMP-140) (13,18,25,26). The selectins are derived from evolutionarily related genes (7,9,18,33,52), and are characterized by a NH2-terminal, Ca-dependent lectin domain, an epidermal growth factor (EGF)-like domain followed by multiple short consensus repeat (SCR) domains, a transmembrane region, and a cytoplasmic tail.L-selectin is expressed on the surface of most leukocytes,

No association between E- and L-selectin genes and SLE: soluble L-selectin levels do correlate with genotype and a subset in SLE

“…Interestingly, sL-selectin may not be a mere bystander in lupus as the soluble form of the molecule has been shown to be functional; for example, it can inhibit lymphocyte migration to peripheral lymph nodes. 15,16 Indeed, abnormal sL-selectin level may predict patients who develop pulmonary inflammation 47,48 and vascular disease including pulmonary hypertension, 49 and ischaemic heart disease. 50 The association of sL-selectin with IgG-ACA in our patients suggests that the soluble molecule may serve as a marker for vascular risk in SLE, and studies are planned to explore this possibility.…”

“…13,14 sL-selectin is present at high concentrations in the serum of healthy humans (B1.0 mg/ml) and retains functional activity perhaps inhibiting interactions involving its cell surface counterpart. 15 Physiological levels of sL-selectin may reduce lymphocyte migration to peripheral lymph nodes by 30%. 16 sE-selectin is also present in serum but at low concentrations.…”

Adhesion molecules in common variable immunodeficiency (CVID)—a decrease inl-selectin-positive T lymphocytes

“…Circulating forms of the same molecules are found in blood, thought to reflect up-regulation and shedding of the same molecules from the cell membrane [19]. In vitro, some of these molecules retain the binding characteristics of their membrane counterparts and have been found to modulate adhesion or cell signalling [20,21].…”

Modulation of neutrophil adherence to endothelial cells by platelet-derived adherence-inhibiting factor through interactions with selectin molecules

“…Moreover, when EC are detached, platelets bind to the basement membrane and express P-selectin on their surfaces [12]. It is interesting to note that soluble L-, P-, and E-selectins are present in human plasma and involved in the regulation of neutrophil adherence [45][46][47]. AIF is localized in lysosomes and is extracellularly released from thrombin-stimulated platelets [14].…”