CDB25:0003463 CXCL2 — ACKR1

Experimentally validated in Mouse; Orthology-inferred in Human, Rat, Chicken, Macaque, Pig, Cow, Chimp, Horse

Title

Journal:; Year Published:

Abstract

Distinct Compartmentalization of the Chemokines CXCL1 and CXCL2 and the Atypical Receptor ACKR1 Determine Discrete Stages of Neutrophil Diapedesis.

Immunity, 2018; PubMed, Mus Musculus Cxcl2 — Mus Musculus Ackr1

ABSTRACT: Neutrophils require directional cues to navigate through the complex structure of venular walls and into inflamed tissues. Here we applied confocal intravital microscopy to analyze neutrophil emigration in cytokine-stimulated mouse cremaster muscles. We identified differential and non-redundant roles for the chemokines CXCL1 and CXCL2, governed by their distinct cellular sources. CXCL1 was produced mainly by TNF-stimulated endothelial cells (ECs) and pericytes and supported luminal and sub-EC neutrophil crawling. Conversely, neutrophils were the main producers of CXCL2, and this chemokine was critical for correct breaching of endothelial junctions. This pro-migratory activity of CXCL2 depended on the atypical chemokine receptor 1 (ACKR1), which is enriched within endothelial junctions. Transmigrating neutrophils promoted a self-guided migration response through EC junctions, creating a junctional chemokine "depot" in the form of ACKR1-presented CXCL2 that enabled efficient unidirectional luminal-to-abluminal migration. Thus, CXCL1 and CXCL2 act in a sequential manner to guide neutrophils through venular walls as governed by their distinct cellular sources.

Basic Information on CXCL2

Ligand Name: C-X-C motif chemokine ligand 2

Other Symbols: GRO2, SCYB2, GROb, MIP-2a, MGSA-b, CINC-2a

Ligand Location: secreted based on perplexity, uniprot

HGNC Gene Symbol Report: CXCL2

GeneCards: CXCL2

HGNC Gene Group: Receptor ligands: Chemokine ligands

Functional Annotations for CXCL2

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Receptors for CXCL2

CXCL2 — CXCR1 ・ CXCL2 — CXCR2

Basic Information on ACKR1

Receptor Name: atypical chemokine receptor 1 (Duffy blood group)

Other Symbols: FY, DARC, CCBP1, GPD, Dfy, CD234

Receptor Location: cell membrane based on perplexity

HGNC Gene Symbol Report: ACKR1

GeneCards: ACKR1

HGNC Gene Group: 7TM proteins, Blood group antigens, CD molecules

Functional Annotations for ACKR1

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Ligands for ACKR1

CCL17 — ACKR1 ・ CCL2 — ACKR1 ・ CCL5 — ACKR1 ・ CCL7 — ACKR1 ・ CCL8 — ACKR1 ・ CXCL1 — ACKR1 ・ CXCL5 — ACKR1 ・ CXCL8 — ACKR1 ・ CCL1 — ACKR1 ・ CCL11 — ACKR1 ・ CCL13 — ACKR1 ・ CCL14 — ACKR1 ・ CCL16 — ACKR1 ・ CCL18 — ACKR1 ・ CXCL10 — ACKR1 ・ CXCL11 — ACKR1 ・ CXCL12 — ACKR1 ・ CXCL13 — ACKR1 ・ CXCL6 — ACKR1 ・ CXCL9 — ACKR1