The transmembrane form of the CX3CL1 chemokine fractalkine is expressed predominantly by epithelial cells in vivo.
Fractalkine (CX3CL1) is synthesized as a type I transmembrane protein. Its unique CX(3)C chemokine domain is attached to a 241-amino acid mucin stalk, a 19-amino acid transmembrane domain, and a 37-amino acid intracellular domain of unknown function. A soluble form of fractalkine can be generated by proteolytic cleavage at the base of the mucin stalk. Novel monoclonal and polyclonal antibodies that specifically recognize only the amino- or carboxyl-terminal ends of the human fractalkine molecule have revealed that epithelial cells are the predominant cell type expressing transmembrane forms of fractalkine in human skin, the tonsil, and the large intestine. Using these specific anti-fractalkine reagents we do not detect high-level expression of fractalkine on endothelial cells in normal or inflamed colon samples obtained from patients with Crohn's disease or ulcerative colitis. In contrast to previous reports we do not detect fractalkine expression by Langerhans cells or immature dendritic cells in mucosal-associated lymphoid tissues in vivo. We show that the reagent used in previous studies, an anti-fractalkine N-terminal peptide antisera, cross-reacts with human CD84. Finally we discuss potential roles for fractalkine in constitutive leukocyte trafficking based on its observed pattern of expression in epithelia.
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
A D
AD
Lucas
N
N
Chadwick
B F
BF
Warren
D P
DP
Jewell
S
S
Gordon
F
F
Powrie
D R
DR
Greaves
D000230:Adenocarcinoma / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000918:Antibody Specificity; D015703:Antigens, CD / Q000276:immunology; D016466:CHO Cells; D002460:Cell Line; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D019743:Chemokines, CXC / Q000276:immunology / Q000378:metabolism*; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism; D006224:Cricetinae; D003429:Cross Reactions; D004817:Epidermis / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism; D007633:Keratins / Q000378:metabolism; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D014066:Palatine Tonsil / Q000378:metabolism; D010455:Peptides / Q000276:immunology; D020033:Protein Isoforms / Q000378:metabolism; D000071176:Signaling Lymphocytic Activation Molecule Family; D014407:Tumor Cells, Cultured
D000906:Antibodies; D015703:Antigens, CD; C498970:CD84 protein, human; C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D019743:Chemokines, CXC; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010455:Peptides; D020033:Protein Isoforms; D000071176:Signaling Lymphocytic Activation Molecule Family; D007633:Keratins