Role of CC chemokines (macrophage inflammatory protein-1 beta, monocyte chemoattractant protein-1, RANTES) in acute lung injury in rats.
The role of the CC chemokines, macrophage inflammatory protein-1 beta (MIP-1 beta), monocyte chemotactic peptide-1 (MCP-1), and RANTES, in acute lung inflammatory injury induced by intrapulmonary deposition of IgG immune complexes injury in rats was determined. Rat MIP-1 beta, MCP-1, and RANTES were cloned, the proteins were expressed, and neutralizing Abs were developed. mRNA and protein expression for MIP-1 beta and MCP-1 were up-regulated during the inflammatory response, while mRNA and protein expression for RANTES were constitutive and unchanged during the inflammatory response. Treatment of rats with anti-MIP-1 beta Ab significantly decreased vascular permeability by 37% (p = 0.012), reduced neutrophil recruitment into lung by 65% (p = 0.047), and suppressed levels of TNF-alpha in bronchoalveolar lavage fluids by 61% (p = 0.008). Treatment of rats with anti-rat MCP-1 or anti-rat RANTES had no effect on the development of lung injury. In animals pretreated intratracheally with blocking Abs to MCP-1, RANTES, or MIP-1 beta, significant reductions in the bronchoalveolar lavage content of these chemokines occurred, suggesting that these Abs had reached their targets. Conversely, exogenously MIP-1 beta, but not RANTES or MCP-1, caused enhancement of the lung vascular leak. These data indicate that MIP-1 beta, but not MCP-1 or RANTES, plays an important role in intrapulmonary recruitment of neutrophils and development of lung injury in the model employed. The findings suggest that in chemokine-dependent inflammatory responses in lung CC chemokines do not necessarily demonstrate redundant function.
Bless
N M
NM
Department of Trauma Surgery, University of Freiburg, Freiburg, Germany.
Huber-Lang
M
M
Guo
R F
RF
Warner
R L
RL
Schmal
H
H
Czermak
B J
BJ
Shanley
T P
TP
Crouch
L D
LD
Lentsch
A B
AB
Sarma
V
V
Mulligan
M S
MS
Friedl
H P
HP
Ward
P A
PA
D000208:Acute Disease; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000936:Antigen-Antibody Complex / Q000633:toxicity; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018932:Chemokine CCL2 / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D019742:Chemokines, CC / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003001:Cloning, Molecular; D007106:Immune Sera / Q000008:administration & dosage; D007074:Immunoglobulin G / Q000633:toxicity; D007442:Intubation, Intratracheal; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D019402:Macrophage Inflammatory Proteins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D008297:Male; D011650:Pulmonary Alveoli / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020318:Rats, Long-Evans; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology
D019138:Antibodies, Blocking; D000936:Antigen-Antibody Complex; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D007106:Immune Sera; D007074:Immunoglobulin G; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins