Expression of the chemokine N51/KC in the thymus and epidermis of transgenic mice results in marked infiltration of a single class of inflammatory cells.
Transgenic mice expressing the chemokine N51/KC in thymus, skin, and tongue showed a marked infiltration of a single class of inflammatory cells (neutrophils) in the sites of transgene expression. In the thymus, neutrophils were most numerous in the cortex and juxta-medullary regions, often forming aggregates or clusters. A similar, but less intense, neutrophilic infiltrate occurred in close proximity to the epidermal basal layer of the tongue and skin. No morphologic evidence of injury was observed in the thymus, skin, or tongue of these transgenic mice, indicating that N51/KC expression induces recruitment but not inflammatory activation of neutrophils. The lack of activation in the thymus resulted in a large senescent neutrophilic population that was phagocytosed by thymic macrophages and epithelial-reticular cells. These results indicate that N51/KC is a neutrophil chemoattractant in vivo and establish these transgenic mice as effective models to study the phenomena of recruitment and clearance of neutrophils, events that are critical for the initiation and resolution of the inflammatory response.
Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543.
S A
SA
Lira
P
P
Zalamea
J N
JN
Heinrich
M E
ME
Fuentes
D
D
Carrasco
A C
AC
Lewin
D S
DS
Barton
S
S
Durham
R
R
Bravo
D000375:Aging / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000096:biosynthesis*; D015870:Gene Expression; D013006:Growth Hormone / Q000096:biosynthesis / Q000235:genetics; D006133:Growth Substances / Q000096:biosynthesis*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000378:metabolism* / Q000502:physiology; D009838:Oligodeoxyribonucleotides; D012867:Skin / Q000378:metabolism*; D013950:Thymus Gland / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D014059:Tongue / Q000378:metabolism
C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D009838:Oligodeoxyribonucleotides; D013006:Growth Hormone