Regulatory effects of eotaxin on acute lung inflammatory injury.
Eotaxin, which is a major mediator for eosinophil recruitment into lung, has regulatory effects on neutrophil-dependent acute inflammatory injury triggered by intrapulmonary deposition of IgG immune complexes in rats. In this model, eotaxin mRNA and protein were up-regulated during the inflammatory response, resulting in eotaxin protein expression in alveolar macrophages and in alveolar epithelial cells. Ab-induced blockade of eotaxin in vivo caused enhanced NF-kappaB activation in lung, substantial increases in bronchoalveolar lavage levels of macrophage inflammatory protein (MIP)-2 and cytokine-induced neutrophil chemoattractant (CINC), and increased MIP-2 and CINC mRNA expression in alveolar macrophages. In contrast, TNF-alpha levels were unaffected, and IL-10 levels fell. Under these experimental conditions, lung neutrophil accumulation was significantly increased, and vascular injury, as reflected by extravascular leak of (125)I-albumin, was enhanced. Conversely, when recombinant eotaxin was administered in the same inflammatory model of lung injury, bronchoalveolar lavage levels of MIP-2 were reduced, as was neutrophil accumulation and the intensity of lung injury. In vitro stimulation of rat alveolar macrophages with IgG immune complexes greatly increased expression of mRNA and protein for MIP-2, CINC, MIP-1alpha, MIP-1beta, TNF-alpha, and IL-1beta. In the copresence of eotaxin, the increased levels of MIP-2 and CINC mRNAs were markedly diminished, whereas MIP-1alpha, MIP-1beta, TNF-alpha, and IL-1beta expression of mRNA and protein was not affected. These data suggest that endogenous eotaxin, which is expressed during the acute lung inflammatory response, plays a regulatory role in neutrophil recruitment into lung and the ensuing inflammatory damage.
Guo
R F
RF
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Lentsch
A B
AB
Warner
R L
RL
Huber-Lang
M
M
Sarma
J V
JV
Hlaing
T
T
Shi
M M
MM
Lukacs
N W
NW
Ward
P A
PA
D000208:Acute Disease; D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology / Q000473:pathology; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000936:Antigen-Antibody Complex / Q000494:pharmacology; D054413:Chemokine CCL11; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D019742:Chemokines, CC; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D007442:Intubation, Intratracheal; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000235:genetics; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020318:Rats, Long-Evans; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D019138:Antibodies, Blocking; D000936:Antigen-Antibody Complex; C515457:Ccl11 protein, mouse; C515458:Ccl11 protein, rat; D054413:Chemokine CCL11; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; C513297:Cxcl1 protein, rat; C404915:Cxcl2 protein, mouse; C513296:Cxcl2 protein, rat; D016207:Cytokines; D006133:Growth Substances; D007074:Immunoglobulin G; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D019402:Macrophage Inflammatory Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha