Background. Using differential display reverse transcriptase-polymerase chain reaction we have recently identified mob-1, the novel rat homologue of the human α-chemokine IP-10, as a highly inducible gene in adult respiratory distress syndrome (ARDS) lungs. The present study aimed to further implicate mob-1 in the pathogenesis of ARDS. Methods. Pulmonary mob-1 mRNA upregulation was confirmed by Northern blot analysis in three different rat models of ARDS-like lung injury and localized to pulmonary macrophages by using in situ hybridization. Also, Escherichia coli-derived recombinant mob-1 (rmob-1) was tested for its properties in relationship to lung injury. Results. In vivo, intratracheal injection of rmob-1 (50 μg/rat) induced pulmonary leuko- sequestration (myeloperoxidase +93 % ± 8 % versus control, p <0.05) with preferential accumulation of neutrophils in bronchoalveolar lavage fluid (36. 0 % ± 1.0% versus 0. 1 % ± 0.1% in controls, p <0. 01). vitro, transwell migration studies demonstrated chemotactic activity of rmob-1 (50 to 100 ng/ml) toward human monocytes (+151% ± 34 % versus rmob-1 vehicle, p <0. 01) and only weak chemotaxis for human neutrophils (+15% ± 0 % versus rmob- 1 vehicle, p <0. 01). Utilizing a rat aortic ring model ex vivo, rmob-1 at 100 ng/ml exerted a very potent inhibitory effect on angiogenesis (-78.7% ± 6.3% versus rmob-1 vehicle, p <0.01), a major component of the resolution phase of ARDS. Conclusions. Taken together, these data support the involvement of mob-1 in the pathogenic mechanisms of ARDS possibly through chemotactic actions on inflammatory cells and modulation of angiogenesis in the recovery phase of the disease.
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