Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis.
Previous reports have identified a circulating pool of CD45(+) collagen I(+) CXCR4(+) (CD45(+)Col I(+)CXCR4(+)) cells, termed fibrocytes, that traffic to areas of fibrosis. No studies have demonstrated that these cells actually contribute to fibrosis, however. Pulmonary fibrosis was originally thought to be mediated solely by resident lung fibroblasts. Here we show that a population of human CD45(+)Col I(+)CXCR4(+) circulating fibrocytes migrates in response to CXCL12 and traffics to the lungs in a murine model of bleomycin-induced pulmonary fibrosis. Next, we demonstrated that murine CD45(+)Col I(+)CXCR4(+) fibrocytes also traffic to the lungs in response to a bleomycin challenge. Maximal intrapulmonary recruitment of CD45(+)Col I(+)CXCR4(+) fibrocytes directly correlated with increased collagen deposition in the lungs. Treatment of bleomycin-exposed animals with specific neutralizing anti-CXCL12 Ab's inhibited intrapulmonary recruitment of CD45(+)Col I(+)CXCR4(+) circulating fibrocytes and attenuated lung fibrosis. Thus, our results demonstrate, we believe for the first time, that circulating fibrocytes contribute to the pathogenesis of pulmonary fibrosis.
Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at University of California, Los Angeles, USA.
Roderick J
RJ
Phillips
Marie D
MD
Burdick
Kurt
K
Hong
Marin A
MA
Lutz
Lynne A
LA
Murray
Ying Ying
YY
Xue
John A
JA
Belperio
Michael P
MP
Keane
Robert M
RM
Strieter
D000199:Actins / Q000378:metabolism; D000818:Animals; D001761:Bleomycin / Q000633:toxicity; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism*; D002633:Chemotaxis / Q000276:immunology; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D017493:Leukocyte Common Antigens / Q000276:immunology; D055370:Lung Injury; D051379:Mice; D016513:Mice, SCID; D009130:Muscle, Smooth / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D019718:Receptors, CXCR4 / Q000378:metabolism; D017463:Receptors, Complement 3b / Q000276:immunology
D000199:Actins; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D024042:Collagen Type I; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4; D017463:Receptors, Complement 3b; D001761:Bleomycin; D017493:Leukocyte Common Antigens