HERBIMYCIN-A ATTENUATES ISCHEMIA-REPERFUSION INDUCED PULMONARY NEUTROPHIL INFILTRATION

Objectives: to determine whether pharmacological induction of heat sho ck proteins (HSPs) by herbimycin-A (a tyrosine-kinase inhibitor) would protect against neutrophil-mediated lung injury in an animal model of lower torso ischaemia-reperfusion. Materials and methods: Sprague-Daw ley rats were randomised into three groups: the control group underwen t midline laparotomy only; the ischaemia-reperfusion (IX) group underw ent laparotomy and clamping of the infrarenal abdominal aorta for 30 m in followed by 2 h of reperfusion; the third group (HerbIR) was pretre ated with herbimycin-A 18 h prior to IX insult. Wet to dry lung weight ratio (W:D), bronchoalveolar lavage protein concentration (BALprot), tissue myeloperoxidase activity (MPO) and bronchoalveolar lavage neutr ophil count (BALPMN) were measured. Heat shack protein 72 (HSP72) expr ession in lung, intestine, mesentery and liver aas measured using West ern immunoblotting. Results: IR resulted in acute lung injury with tis sue oedema (W:D) and neutrophil infiltration (PMO, BPLPMN). Herbimycin -A, in vivo, induced HSP expression and attenuated neutrophil infiltra tion (MPO, BALPMN). Conclusion: these data indicate that herbimycin-A protects against ischaemia-reperfusion induced pulmonary neutrophil in filtration, possibly by increasing the expression of heat shock protei ns.