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Mucosal basophils, eosinophils, and mast cells
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Edda Fiebiger, Stephan C. Bischoff
The recruitment of eosinophils to mucosal sites is also critically dependent on the local production of chemoattractants, especially chemokines. Eotaxin-1 (CCL11) is the most important and selective eosinophil chemoattractant. Eotaxin-1 is responsible for the physiologic recruitment of eosinophils to the intestines in healthy individuals, and is expressed constitutively in the intestinal lamina propria. In the absence of eotaxin-1, or its eosinophil receptor, CCR3, eosinophils fail to home to the gastrointestinal tract. Eosinophils also express the mucosal integrin α4β7 on their cell surface, which is responsible for the selective recruitment of these leukocytes toward the mucosa of the intestines rather than other tissue compartments. Integrin α4β7 binds to its specific ligand, MAdCAM-1 (mucosal vascular addressin cell adhesion molecule-1), which is preferentially expressed on the vascular endothelium of intestinal lamina propria venules.
The Role of Human Genetics in HIV-1 Infection
Published in Thomas R. O’Brien, Chemokine Receptors and AIDS, 2019
Maureen P. Martin, Mary Carrington
The CCR5 gene has been mapped to the short arm of chromosome 3 within a chemokine receptor gene cluster that includes CCR1, CCR2, CCR3, CCR4, CCR6, CCR8, and CX3CR1 (58–60). The CCR5 gene became an obvious disease gene candidate for HIV-1 infection upon the discovery of CCR5 as a co-receptor for HIV-1 and screening the coding region of the gene was easily performed since it contains a single open reading frame (exon 4) of only 1,055 base pairs. A common, severe mutation characterized by a 32 base pair deletion, CCR5-Δ32, was rapidly identified (8–10). The deletion begins in the region encoding the third extracellular domain of CCR5, and results in a frame shift and premature stop codon in the fifth transmembrane domain. The truncated protein product is not expressed on the cell surface (9), explaining the nearly complete protection against HIV-1 infection (see Table 1), despite repeated exposures, in individuals homozygous for the mutant allele (8–10,61,62). Accordingly, peripheral blood lymphocytes (PBLs) from individuals homozygous for CCR5-Δ32 are resistant to infection with R5 (but not X4) strains of HIV-1 in vitro (9,10,63,64). The normal CCR5 function appears to be dispensable, perhaps because of the redundancy of the chemokine receptor system, since individuals who are homozygous for the CCR5-Δ32 are generally unremarkable (see Chapter 10).
Lymphocyte homing and immunology of extranodal lymphoid tissues
Published in Franco Cavalli, Harald Stein, Emanuele Zucca, Extranodal Lymphomas, 2008
Mariagrazia Uguccioni, James J Campbell, Katrin Kuscher, Marshall E Kadin
Allergic insult of the lung leads to a coordinated recruitment of eosinophils. Upon such insult, lung tissue produces the cytokine interleukin-5 (IL-5), along with eotaxin chemokines, which are three closely related chemokines, CCL11,52,53 CCL24,54 and CCL26,55,56 whose only known receptor (as agonists) is CCR3. Eosinophils express CCR3 and specific receptors for IL-5, and functional blockade of either the IL-5 receptor or CCR3 inhibits eosinophil accumulation in lung.57
Obesity, Inflammation, and Advanced Prostate Cancer
Published in Nutrition and Cancer, 2021
Armando Olivas, Ramona Salcedo Price
Adipokines, particularly the C-C chemokine receptor type 3 (CCR3)/C-C motif chemokine ligand 7 (CCL7) signaling axis, have been implicated in the link between obesity and increased metastatic capacity of PCa tumors. Recent In Vivo and In Vitro research demonstrates the adipokine CCL7, also referred to as monocyte-chemotactic protein (MCP)-3, can passively diffuse into the prostate peripheral zone and establishing a chemotactic gradient capable of attracting PCa tumor cells expressing the CCL7 receptor, CCR3 (39). The chemotactic gradient established by the invading adipokine facilitates tumor cell escape from prostate confinement and may be particularly amplified in a state of obesity as hypertrophic adipocytes are capable of secreting larger amounts of adipokines (39). It should be noted the CCR3/CCL7 signaling axis has also been implicated in metastasis in other cancer types as well and CCR3 expression correlates with Gleason score, biochemical recurrence, and surgical treatment failure of PCa (39,40). Furthermore, the proximity of PPAT to the prostate may potentiate the chemotactic effect of CCL7. As previously discussed, the obesity-associated pro-inflammatory cytokines IL-6, IL-1β, and TNFα, all to be discussed below, are also capable of mediating disease progression.
Macrophage targeted nanocarrier delivery systems in HIV therapeutics
Published in Expert Opinion on Drug Delivery, 2020
Tabassum Khan, Mayuresh Mayuresh Patkar, Munira Momin, Abdelwahab Omri
Tat is a viral pleiotropic protein that modifies HIV life cycle through regulation of host cellular and viral gene expression. Expression of TAT protein is important in replication, transcription and release of new viruses. TAT protein is also known to activate monocytes, macrophages, and microglia [24]. Expression of TAT leads to co-expression of HIV co-receptors like CXCR4, CCR3, and CCR5 in macrophages and stimulates HIV infection [25]. Apart from binding interaction, these chemokines also chemotactically recruits other myeloid immune cell types including monocytes, dendritic cells, and macrophages [26,27]. This recruitment of macrophages in HIV-microenvironment triggers release of pro-inflammatory proteins like tumor necrosis factor alpha (TNF-α), which is NF-κB dependent [28]. The activation of NF-κB induces secretion and increase in levels of phospholipase C (PLC), protein tyrosine kinase, protein kinase A secretion and Ca2+ levels. This eventually leads to HIV induced inflammation and neuropathogenesis [23,29].
Factors associated with the activity and severity of bullous pemphigoid: a review
Published in Annals of Medicine, 2020
Yangchun Liu, Yiman Wang, Xinyi Chen, Hongzhong Jin, Li Li
The level of chemokines is determined using ELISA kits. Eotaxin-1 (CCL11) and eotaxin-3 (CCL26) belong to the eotaxin subfamily of CC-chemokines, and their expression is up-regulated in the serum and blister fluid of BP patients. CCL26 is also expressed strongly in the lesions of BP patients. CCL11 and CCL26 are associated significantly with eosinophil activation, especially serum levels of CCL26, which has a close correlation with eosinophil numbers in peripheral blood. Hence, CCL26 levels could be useful for assessing BP activity, and have a role in BP development. Blockade of CCL26 function could provide a novel target for treating BP [30]. CCL11 can bind to the CCR3 expressed on eosinophils and induce eosinophil chemotaxis [31]. In addition, several observations presented that levels of eotaxin, IL-5 and CCR3 were increased in the blister fluid as well as the lesional and peri-lesional skin of BP patients. These markers also have a significant correlation with the number of dermal-infiltrating eosinophils [22,32]. There had been a pilot phase 2a study proving that bertilimumab, an anti-eotaxin-1 antibody, was safe and efficacious in the treatment of BP. This finding provided a novel target for treating BP, however, a larger controlled trial would be expected [33].