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| 1 | Neutrophil chemoattractant receptors in health and disease: double-edged swords显示文摘Neutrophils are frontline cells of the innate immune system.These effector leukocytes are equipped with intriguing antimicrobial machinery and consequently display high cytotoxic potential.Accurate neutrophil recruitment is essential to combat microbes and to restore homeostasis,for inflammation modulation and resolution,wound healing and tissue repair.After fulfilling the appropriate effector functions,however,dampening neutrophil activation and infiltration is crucial to prevent damage to the host.In humans,chemoattractant molecules can be categorized into four biochemical families,i.e.,chemotactic lipids,formyl peptides,complement anaphylatoxins and chemokines.They are critically involved in the tight regulation of neutrophil bone marrow storage and egress and in spatial and temporal neutrophil trafficking between organs.Chemoattractants function by activating dedicated heptahelical G protein-coupled receptors(GPCRs).In addition,emerging evidence suggests an important role for atypical chemoattractant receptors(ACKRs)that do not couple to G proteins in fine-tuning neutrophil migratory and functional responses.The expression levels of chemoattractant receptors are dependent on the level of neutrophil maturation and state of activation,with a pivotal modulatory role for the(inflammatory)environment.Here,we provide an overview of chemoattractant receptors expressed by neutrophils in health and disease.Depending on the(patho)physiological context,specific chemoattractant receptors may be up-or downregulated on distinct neutrophil subsets with beneficial or detrimental consequences,thus opening new windows for the identification of disease biomarkers and potential drug targets. | Mieke Metzemaekers Mieke Gouwy Paul Proost | 2020 | Cellular & Molecular Immunology2020，17，5： | 8 |
| 2 | The chemokines CXCL8 and CXCL12:molecular and functional properties,role in disease and efforts towards pharmacological intervention显示文摘Chemokines are an indispensable component of our immune system through the regulation of directional migration and activation of leukocytes.CxCL8 is the most potent human neutrophil-attracting chemokine and plays crucial roles in the response to infection and tissue injury.CXCL8 activity inherently depends on interaction with the human CXC chemokine receptors CXCR1 and CXCR2,the atypical chemokine receptor ACKR1,and glycosaminoglycans.Furthermore,(hetero)dimerization and tight regulation of transcription and translation,as well as post-translational modifications further fine-tune the spatial and temporal activity of CXCL8 in the context of inflammatory diseases and cancer.The CxCL8 interaction with receptors and glycosaminoglycans is therefore a promising target for therapy,as illustrated by multiple ongoing clinical trials.CXCL8-mediated neutrophil mobilization to blood is directly opposed by CXCL12,which retains leukocytes in bone marrow.CXCL12 is primarily a homeostatic chemokine that induces migration and activation of hematopoietic progenitor cells,endothelial cells,and several leukocytes through interaction with CXCR4,ACKR1,and ACKR3.Thereby,it is an essential player in the regulation of embryogenesis,hematopoiesis,and angiogenesis.However,CXCL12 can also exert inflammatory functions,as illustrated by its pivotal role in a growing list of pathologies and its synergy with CXCL8 and other chemokines to induce leukocyte chemotaxis.Here,we review the plethora of information on the CXCL8 structure,interaction with receptors and glycosaminoglycans,different levels of activity regulation,role in homeostasis and disease,and therapeutic prospects.Finally,we discuss recent research on CXCL12 biochemistry and biology and its role in pathology and pharmacology. | Seppe Cambier Mieke Gouwy Paul Proost | 2023 | Cellular & Molecular Immunology2023，20，3： | 4 |
| 3 | Chemoattractants and cytokines in primary ciliary dyskinesia and cystic fibrosis: key players in chronic respiratory diseases显示文摘Patients with primary ciliary dyskinesia(PCD)and cystic fibrosis(CF),two inherited disorders,suffer from recurrent airway infections characterized by persistent bacterial colonization and uncontrollable inflammation.Although present in high counts,neutrophils fail to clear infection in the airways.High levels of C-X-C motif chemokine ligand 8/interleukin-8(CXCL8/IL-8),the most potent chemokine to attract neutrophils to sites of infection,are detected in the sputum of both patient groups and might cause the high neutrophil influx in the airways.Furthermore,in CF,airway neutrophils are highly activated because of the genetic defect and the high levels of proinflammatory chemoattractants and cytokines(e.g.,CXCL8/IL-8,tumor necrosis factor-αand IL-17).The overactive state of neutrophils leads to lung damage and fuels the vicious circle of infection,excessive inflammation and tissue damage.The inflammatory process in CF airways is well characterized,whereas the lung pathology in PCD is far less studied.The knowledge of CF lung pathology could be useful to guide molecular investigations of the inflammatory processes in PCD lungs.Current available therapies can not completely remedy the chronic airway infections in these diseases.This review gives an overview of the role that chemoattractants and cytokines play in these neutrophil-dominated lung pathologies.Finally,the most frequently applied treatments in CF and PCD and new experimental therapies to reduce neutrophil-dominated airway inflammation are described. | Maaike Cockx Mieke Gouwy Jo Van Damme Sofie Struyf | 2018 | Cellular & Molecular Immunology2018，15，4： | 3 |
| 4 | Synergy in cytokine and chemokine networks amplifies the inflammatory response显示文摘 | Mieke Gouwy Sofie Struyf Paul Proost | 2005 | Cytokine & Growth Factor2005，16，6： | 1 |
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