Impaired pulmonary host defense in mice lacking expression of the CXC chemokine lungkine.
Lungkine (CXCL15) is a novel CXC chemokine that is highly expressed in the adult mouse lung. To determine the biologic function of Lungkine, we generated Lungkine null mice by targeted gene disruption. These mice did not differ from wild-type mice in their hematocrits or in the relative number of cells in leukocyte populations of peripheral blood or other tissues, including lung and bone marrow. However, Lungkine null mice were more susceptible to Klebsiella pneumonia infection, with a decreased survival and increased lung bacterial burden compared with infected wild-type mice. Histologic analysis of the lung and assessment of leukocytes in the bronchioalveolar lavage revealed that neutrophil numbers were normal in the lung parenchyma, but reduced in the airspace. The production of other neutrophil chemoattractants in the Lungkine null mice did not differ from that in wild-type mice, and neutrophil migration into other tissues was normal. Taken together, these findings demonstrate that Lungkine is an important mediator of neutrophil migration from the lung parenchyma into the airspace.
Chen
S C
SC
Department of Immunology, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Mehrad
B
B
Deng
J C
JC
Vassileva
G
G
Manfra
D J
DJ
Cook
D N
DN
Wiekowski
M T
MT
Zlotnik
A
A
Standiford
T J
TJ
Lira
S A
SA
D000818:Animals; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines / Q000032:analysis; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D002630:Chemotactic Factors / Q000032:analysis; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D018390:Gene Targeting; D020022:Genetic Predisposition to Disease; D006133:Growth Substances / Q000032:analysis; D007113:Immunity, Innate / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins; D007711:Klebsiella pneumoniae / Q000276:immunology; D007958:Leukocyte Count; D008168:Lung / Q000166:cytology / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009503:Neutropenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; C118893:Cxcl15 protein, mouse; C404915:Cxcl2 protein, mouse; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha