Expression of the neutrophil chemoattractant interleukin-8 in the lesions of bovine pneumonic pasteurellosis.
We investigated the expression of interleukin-8 (IL-8) in pneumonic pasteurellosis of cattle because neutrophils are important mediators of tissue injury in this disease and because IL-8 is a major neutrophil chemoattractant in other species. We also compared IL-8 expression in bacterial and viral pneumonia, since the latter lacks the severe neutrophil exudation typical of pneumonic pasteurellosis. IL-8 expression was assessed by northern analysis, in situ hybridization, enzyme-linked immunosorbent assay, and in vivo bioassay. IL-8 mRNA expression was elevated dramatically in lesions of pneumonic pasteurellosis compared to unaffected lung from the same calves. In situ hybridization revealed intense expression of IL-8 mRNA in alveolar macrophages and neutrophils and milder expression in bronchiolar and alveolar epithelium, interstitial cells, and pleural mesothelium. Bronchoalveolar lavage fluid from lesional lung contained 16.06+/-4.00 ng/ml IL-8, whereas those from nonlesional and normal lung contained 0.34+/-0.11 and 0.01+/-0.002 ng/ml, respectively. We detected IL-8 expression at only minimal levels in bovine respiratory syncytial viral pneumonia. Lung extracts from lesions of pneumonic pasteurellosis induced vigorous neutrophil infiltration following injection into bovine skin, and 89% depletion of IL-8 from the extract reduced this neutrophil influx by 60%. These results demonstrate consistent upregulation of IL-8 expression in lesions of pneumonic pasteurellosis, implying a role for IL-8 in the ongoing recruitment of neutrophils to established lesions of pneumonic pasteurellosis. Because neutrophil-mediated tissue injury is critical to the pathogenesis of pneumonic pasteurellosis, these data suggest that neutralization of IL-8 activity could ameliorate the severe clinical signs and lesions of this disease.
Caswell
J L
JL
Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada. caswell@admin3.usask.ca
Middleton
D M
DM
Sorden
S D
SD
Gordon
J R
JR
D000818:Animals; D015152:Blotting, Northern / Q000662:veterinary; D018893:Bronchoalveolar Lavage / Q000662:veterinary; D002417:Cattle; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D005786:Gene Expression Regulation; D017403:In Situ Hybridization / Q000662:veterinary; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D007428:Intradermal Tests / Q000662:veterinary; D008168:Lung / Q000276:immunology* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000473:pathology; D016978:Mannheimia haemolytica / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D012766:Pasteurellosis, Pneumonic / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000473:pathology / Q000662:veterinary; D018112:Respiratory Syncytial Virus, Bovine / Q000276:immunology
D016209:Interleukin-8; D012333:RNA, Messenger