Granulocyte-macrophage colony-stimulating factor amplifies lipopolysaccharide-induced bronchoconstriction by a neutrophil- and cyclooxygenase 2-dependent mechanism

Citation
L. Wollin et al., Granulocyte-macrophage colony-stimulating factor amplifies lipopolysaccharide-induced bronchoconstriction by a neutrophil- and cyclooxygenase 2-dependent mechanism, AM J R CRIT, 163(2), 2001, pp. 443-450
Citations number
36
Categorie Soggetti
Cardiovascular & Respiratory Systems","da verificare
Journal title
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
ISSN journal
1073449X → ACNP
Volume
163
Issue
2
Year of publication
2001
Pages
443 - 450
Database
ISI
SICI code
1073-449X(200102)163:2<443:GCFAL>2.0.ZU;2-O
Abstract
Granulocyte-macrophage colony-stimulating factor (CM-CSF) is used to amelio rate neutropenia in patients after antineoplastic treatment. It has also be en suggested as an adjunct treatment in septic patients; however, the recru itment and priming of leukocytes by CM-CSF bears the hazard of a hyperinfla mmatory response. In particular, the role of CM-CSF in pulmonary functions in septic lungs is still unclear. Therefore, we pretreated rats in vivo wit h CM-CSF (50 mug/kg, intravenous) and assessed the pulmonary functions of t heir subsequently prepared isolated perfused lungs when exposed to subtoxic concentrations of lipopolysaccharide (LPS, 2 mug/ml), These lungs showed e nhanced expression of cy clooxygenase 2 (COX-2), a significant increase in thromboxane (TX) and tumor necrosis factor (TNF) release into the venous pe rfusate, and bronchoconstriction. COX-2 inhibition or blocking of the TX re ceptor abolished the CM-CSF/LPS-induced bronchoconstriction, but not the TN F release. Neutralizing antibodies against TNF did not prevent CM-CSF/LPS-i nduced bronchoconstriction. After CM-CSF pretreatment, massive neutrophil i nvasion into the lung occurred. Neutropenic rats were protected against CM- CSF/LPS-induced lung injury. Similar results were obtained in rats pretreat ed with C-CSF instead of CM-CSF. We conclude that GM-CSF pretreatment exace rbates pulmonary injury by low-dose LPS via COX-2 expression, TX release, a nd bronchoconstriction by initiating neutrophil invasion and activation.