Expression and biologic characterization of the murine chemokine KC.
KC, the product of an immediate early gene induced in mouse fibroblasts by platelet-derived growth factor, was expressed in Escherichia coli by using a maltose binding protein vector and biochemically characterized as a ligand for both murine and human polymorphonuclear neutrophils (PMN). On murine PMN, KC is both a potent chemoattractant and up-regulator of Mac-1 cell surface expression. On human PMN, in contrast, KC exhibits dissociation of its chemoattractant and Mac-1 up-regulatory activities. Although KC strongly increases Mac-1 expression on human PMN, it does not induce chemotaxis in vitro. 125I-KC-Tyr binds to both mouse and human PMN with two classes of binding sites, including high affinity sites of 0.8 and 2 nM, with approximately 9,000 and 10,000 sites per cell, respectively. On mouse PMN, human macrophage inflammatory protein (MIP)-2 alpha and MIP-2 beta compete for 125I-KC-Tyr binding with high affinity, whereas the murine beta-chemokine TCA-3 does not compete. KC binds to human PMN by the IL-8 type B receptor and to murine PMN by a murine IL-8 type B receptor homologue. 125I-KC-Tyr also binds to human RBC with a single class of high affinity sites. KC mRNA is constitutively expressed in multiple murine tissues. With human IL-8 and KC cDNA as probes, a mouse neutrophil exudate library was screened: KC and MIP-2 were the dominant chemokine species found. Thus, KC appears to be intimately involved in murine inflammation and its constitutive expression may have a role in the basal trafficking of neutrophils.
Bozic
C R
CR
Ina Sue Perlmutter Laboratory, Children's Hospital, Boston, MA 02115, USA.
Kolakowski
L F
LF
Gerard
N P
NP
Garcia-Rodriguez
C
C
von Uexkull-Guldenband
C
C
Conklyn
M J
MJ
Breslow
R
R
Showell
H J
HJ
Gerard
C
C
D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology; D001483:Base Sequence; D002478:Cells, Cultured; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology* / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D051379:Mice; D008969:Molecular Sequence Data; D015846:Monokines / Q000502:physiology; D009504:Neutrophils / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics; D023062:Receptors, Interleukin-8A; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection / Q000235:genetics
D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; D016207:Cytokines; D018836:Inflammation Mediators; D016177:Macrophage-1 Antigen; D015846:Monokines; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D011994:Recombinant Proteins; C074302:keratinocyte-derived chemokines