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| 1 | The unique structural and functional features of CXCL12显示文摘The CXC chemokine CXCL12 is an important factor in physiological and pathological processes, includingembryogenesis, hematopoiesis, angiogenesis and inflammation, because it activates and/or induces migration ofhematopoietic progenitor and stem cells, endothelial cells and most leukocytes. Therefore, CXCL12 activity istightly regulated at multiple levels. CXCL12 has the unique property of existing in six splice variants in humans,each having a specific tissue distribution and in vivo activity. Controlled splice variant transcription and mRNAstability determine the CXCL12 expression profile. CXCL12 fulfills its functions in homeostatic and pathologicalconditions by interacting with its receptors CXC chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3(ACKR3) and by binding to glycosaminoglycans (GAGs) in tissues and on the endothelium to allow a properpresentation to passing leukocytes. Homodimerizaton and heterodimerization of CXCL12 and its receptors can altertheir signaling activity, as exemplified by the synergy between CXCL12 and other chemokines in leukocyte migrationassays. Receptor binding may also initiate CXCL12 internalization and its subsequent removal from theenvironment. Furthermore, CXCL12 activity is regulated by posttranslational modifications. Proteolytic removal ofNH2- or COOH-terminal amino acids, citrullination of arginine residues by peptidyl arginine deiminases or nitrationof tyrosine residues reduce CXCL12 activity. This review summarizes the interactions of CXCL12 with the cellularenvironment and discusses the different levels of CXCL12 activity regulation. | Rik Janssens Sofie Struyf Paul Proost | 2018 | Cellular & Molecular Immunology2018，15，4： | 28 |
| 2 | 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 |
| 3 | 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 |
| 4 | Neutrophil gelatinase B potentiates intedeukin - 8 tenfold by aminoterminal processing, whereas it degrades CTAP - Ⅲ, PF - 4,and GRO- α and RANTES and MCP- 2 intact显示文摘 | Philippe E Van den Steen Paul Proost | 2000 | Blood2000，96，8： | 1 |
| 5 | 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 |
| 6 | Ferritin acts as a target site for the snowdrop lectin (GNA) in the midgut of the cotton leafworm Spodoptera littoralis显示文摘雪花莲 lectin GNA (Galanthus 雪是凝集素) 被显示了拥有杀虫的活动到经济地重要的昆虫害虫的一个范围。然而,对昆虫的 GNA 的杀虫的行动的精确机制仍然保持未知。在这调查,我们试图在一个主要鳞翅类的害虫的幼虫的中间的内脏净化并且识别为 GNA 的绑定负责的受体(棉花叶蠕虫, Spodoptera 沿岸) 更好理解它行动的模式。因此,象从 800 口幼虫的中间的勇气的膜蛋白质一样细胞质与使不能调动的 GNA 在列上被用色层法分离。从GNA有约束力的蛋白质和强风分析定序跟随的 GNA 列的蛋白质 eluted 的钠 dodecyl sulfate-polyacrylamide 胶化电气泳动分析表明 24 kDa 多肽的N终端序列净化了从细胞质并且膜蛋白质部分揭示顺序类似到从 Manduca 编码含铁锡的重链相当或相同的事物的序列祷告一(76%顺序身份), Calpodes ethlius (80%顺序身份)和 Bombyx 粗腐殖质 i (61%顺序身份)。而且,从膜蛋白质部分的 31 kDa 多肽的 N 终端顺序从 Manduca 祷告显示出顺序类似到含铁锡的一个轻链相当或相同的事物一(88% 顺序身份) 。 | Amin Sadeghi Guy Smagghe Paul Proost Els J.M. Van Damme | 2008 | Insect Science2008，15，6： | 1 |
| 7 | Neut rophilgelatinase B protentiates interleukn28 tenfold by amino terminal processing , whereas it degrades CTAP- III, PF-4and GRO-a and RANTES and MCP-2 intact 显示文摘 | Philippe E Vanden Steen Paul Proost | 2000 | Blood2000，96，8： | 1 |
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