Monocytes are potent facilitators of alveolar neutrophil emigration during lung inflammation: role of the CCL2-CCR2 axis.
Coordinated neutrophil and monocyte recruitment is a characteristic feature of acute lung inflammatory responses. We investigated the role of monocyte chemotactic protein-1 (CCL2, JE) and the chemokine receptor CCR2 in regulating alveolar leukocyte traffic. Groups of wild-type (WT) mice, CCR2-deficient mice, lethally irradiated CCR2-deficient and WT mice that were reciprocally bone marrow transplanted (chimeric CCR2 deficient and WT, respectively), chimeric CCR2-deficient mice with an enriched CCR2(+) alveolar macrophage population, and CCR2-deficient mice transfused with CCR2(+) mononuclear cells were treated with intratracheal CCL2 and/or Escherichia coli endotoxin. Our data show that alveolar monocyte recruitment is strictly dependent on CCR2. LPS-induced neutrophil migration to the lungs is CCR2 independent. However, when CCR2-bearing blood monocytes are present, alveolar neutrophil accumulation is accelerated and drastically amplified. We suggest that this hitherto unrecognized cooperativity between monocytes and neutrophils contributes to the strong, coordinated leukocyte efflux in lung inflammation.
Maus
Ulrich A
UA
Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine and Infectious Diseases, Justus-Liebig-University, Giessen, Germany. Ulrich.A.Maus@med.uni-giessen.de
Waelsch
Katharina
K
Kuziel
William A
WA
Delbeck
Tim
T
Mack
Matthias
M
Blackwell
Timothy S
TS
Christman
John W
JW
Schlöndorff
Detlef
D
Seeger
Werner
W
Lohmeyer
Jürgen
J
D019264:Adoptive Transfer; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D016026:Bone Marrow Transplantation; D018932:Chemokine CCL2 / Q000097:blood / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000276:immunology* / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology* / Q000637:transplantation; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology*; D011650:Pulmonary Alveoli / Q000276:immunology* / Q000473:pathology*; D011828:Radiation Chimera / Q000276:immunology; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000502:physiology*
C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D008070:Lipopolysaccharides; D054390:Receptors, CCR2; D019707:Receptors, Chemokine