Cloning and characterization of exodus, a novel beta-chemokine.
Chemokines are a family of related proteins that regulate leukocyte infiltration into inflamed tissue. Some chemokines such as MIP-1 alpha also inhibit hematopoietic progenitor cell proliferation. Recently, three chemokines, MIP-1 alpha, MIP-1 beta, and RANTES, have been found to significantly decrease human immunodeficiency virus production from infected T cells. We report here the cloning and characterization of a novel human chemokine termed Exodus for its chemotactic properties. This novel chemokine is distantly related to other chemokines (28% homology with MIP-1 alpha) and shares several biological activities. Exodus is expressed preferentially in lymphocytes and monocytes, and its expression is markedly upregulated by mediators of inflammation such as tumor necrosis factor or lipopolysaccharide. Purified synthetic Exodus was found to inhibit proliferation of myeloid progenitors in colony formation assays. Exodus also stimulated chemotaxis of peripheral blood mononuclear cells. The sequence homology, expression, and biological activity indicate that Exodus represents a novel divergent beta-chemokine.
Hromas
R
R
Department of Hematology/Oncology and the Walther Oncology Center, Indiana University Medical Center, Indianapolis 46202, USA.
Gray
P W
PW
Chantry
D
D
Godiska
R
R
Krathwohl
M
M
Fife
K
K
Bell
G I
GI
Takeda
J
J
Aronica
S
S
Gordon
M
M
Cooper
S
S
Broxmeyer
H E
HE
Klemsz
M J
MJ
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D001854:Bone Marrow Cells; D002460:Cell Line; D054418:Chemokine CCL20; D018925:Chemokines / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D019742:Chemokines, CC; D002633:Chemotaxis / Q000187:drug effects; D003001:Cloning, Molecular; D018076:DNA, Complementary; D015723:Gene Library; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism*; D007700:Kinetics; D019402:Macrophage Inflammatory Proteins; D008969:Molecular Sequence Data; D009928:Organ Specificity; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D018925:Chemokines; D019742:Chemokines, CC; D018076:DNA, Complementary; D019402:Macrophage Inflammatory Proteins; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D011994:Recombinant Proteins