Mucin-Like Domain of Mucosal Addressin Cell Adhesion Molecule-1 Facilitates Integrin α4β7-Mediated Cell Adhesion Through Electrostatic Repulsion

Abstract

The homing of lymphocytes from blood to gut-associated lymphoid tissue is regulated by interaction between integrin α4β7 with mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) expressed on the endothelium of high endothelial venules (HEVs). However, the molecular basis of mucin-like domain, a specific structure of MAdCAM-1 regulating integrin α4β7-mediated cell adhesion remains obscure. In this study, we used heparan sulfate (HS), which is a highly acidic linear polysaccharide with a highly variable structure, to mimic the negative charges of the extracellular microenvironment and detected the adhesive behaviors of integrin α4β7 expressing 293T cells to immobilized MAdCAM-1 in vitro. The results showed that HS on the surface significantly promoted integrin α4β7-mediated cell adhesion, decreased the percentage of cells firmly bound and increased the rolling velocities at high wall shear stresses, which was dependent on the mucin-like domain of MAdCAM-1. Moreover, breaking the negative charges of the extracellular microenvironment of CHO-K1 cells expressing MAdCAM-1 with sialidase inhibited cell adhesion and rolling velocity of 293T cells. Mechanistically, electrostatic repulsion between mucin-like domain and negative charges of the extracellular microenvironment led to a more upright conformation of MAdCAM-1, which facilitates integrin α4β7-mediated cell adhesion. Our findings elucidated the important role of the mucin-like domain in regulating integrin α4β7-mediated cell adhesion, which could be applied to modulate lymphocyte homing to lymphoid tissues or inflammatory sites.

Lncap-AI prostate cancer cell line establishment by Flutamide and androgen-free environment to promote cell adherent

“…Cell adhesion function could be used in multiple physiological and pathological processes, such as embryonic development and differentiation, maintenance of normal tissue structure, inflammatory response, immune response, clotting and thrombosis, trauma repair, tumor immersion and metastasis, and embryo occurrence. Cell adhesion is also an important character in the hallmark of cancer, which has a strong relationship with metastasis [9][10][11]. At present, the cell adhesion mechanism has become one of the hot spots in cancer cell invasion and metastasis research.…”

Nanoplastics Affect the Bioaccumulation and Gut Toxicity of Emerging Perfluoroalkyl Acid Alternatives to Aquatic Insects (Chironomus kiinensis): Importance of Plastic Surface Charge

“…According to the relationship between the mortality of C. kiinensis and the dissolved F-53B concentration, the F NPs were calculated as 19.6% for F-53B associated with positively charged NPs and 13.6% for F-53B associated with negatively charged NPs, indicating that NP-associated F-53B possessed bioavailability to C. kiinensis and that positively charged NP-associated F-53B possessed a higher bioavailable fraction than negatively charged NP-associated F-53B. This finding may attribute to that positively charged NPs (adsorption of F-53B does not change the surface charge of NPs) can transport across the cell membrane with negatively charge more easily − through membrane penetration, further increasing the probability of F-53B interacting with cell membranes and enhancing bioavailability to organisms.…”

“…Thus, positively charged NPs caused higher accumulation of F-53B in the larvae than the negatively charged one, leading to stronger gut toxicity in the exist of positively charged NPs. In addition, positively charged NPs (adsorption of F-53B does not change the surface charge of NPs) interact and internalize more easily with negatively charged gut biomembranes − (such as epithelial cells and DAO-producing cells) through membrane penetration; positively charged NPs can transport across the cell membrane more easily and induce stronger tension on the microbial cell membrane than negatively charged NPs, , further increasing the probability of F-53B interacting with gut biomembranes and microbiota. Therefore, positively charged NPs enhanced the adverse impacts on gut health and growth of C. kiinensis induced by F-53B compared with negatively charged NPs.…”

Differentially Charged Nanoplastics Induce Distinct Effects on the Growth and Gut of Benthic Insects (Chironomus kiinensis) via Charge-Specific Accumulation and Perturbation of the Gut Microbiota

“…26,27 Generally, the cell membrane 28 and bacteria 29 usually carry a negative surface charge, which mainly comes from phospholipids and glycosylation of extracellular domains of cell membrane proteins. 30 Moreover, positively charged NPs are usually more stable in the medium. 31 Hence, we hypothesized that positively charged NPs will induce stronger gut damage and microbial perturbation of Chironomus kiinensis larvae than negatively charged NPs.…”

“…Because the digestion of MPs/NPs by aquatic organisms is very limited, ingested MPs/NPs can stay in the gut for a long time and disrupt the gut barrier in aquatic animals, inducing gut inflammatory responses and changing the membrane permeability of the gut epithelial cells of aquatic animals, thus posing a potential threat to benthic insect health. Furthermore, the gut microbiota benefits host health by participating in nutrient digestion and absorption, constructing the gut immune barrier, and resisting external stimuli. , Nevertheless, the gut flora of zoobenthos can be affected by external contaminants. , Generally, the cell membrane and bacteria usually carry a negative surface charge, which mainly comes from phospholipids and glycosylation of extracellular domains of cell membrane proteins . Moreover, positively charged NPs are usually more stable in the medium .…”