Induction of Cytokine-Induced Neutrophil Chemoattractant (CINC) mRNA in the Lungs of Septic Rats

Abstract

To study cytokine-induced neutrophil chemoattractant (CINC) mRNA induction in lungs of normal, neutropenic, and adrenalectomized rats after intraperitoneal Escherichia coli lipopolysaccharide (LPS) administration and in cultured rat pulmonary cell lines after exposure to mediators of the septic response. Northern blotting was used to assay relative CINC mRNA levels and a colorimetric myeloperoxidase assay was used as a measure of neutrophil infiltration. After a single dose of LPS, rapid induction of CINC mRNA coincided with neutrophil infiltration into lungs, a response that lasted approximately 12 to 24 hours. Multiple LPS treatments resulted in a similar CINC response, but a more prolonged myeloperoxidase response. CINC mRNA induction in lungs was heightened 30% in adrenalectomized animals and 400% in neutropenic ones. LPS and cytokines induced CINC mRNA in cultured endothelial and epithelial cells. Induction of CINC mRNA expression in pulmonary endothelial and/or epithelial cells by systemic LPS or cytokines may play a role in mediating neutrophil infiltration into lungs during sepsis. Markedly increased CINC induction in the lungs of neutropenic animals suggests that neutrophils may act to inhibit expression of this chemoattractant via a negative feedback mechanism.