THE NOVEL CHEMOKINE MOB-1 - INVOLVEMENT IN ADULT-RESPIRATORY-DISTRESS-SYNDROME

Background. Using differential display reverse transcriptase-polymeras e chain reaction we have recently identified mob-1, the novel rat homo logue of the human alpha-chemokine IP-10, as a highly inducible gene i n 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 up-regulation was confirmed by Northern blot ana lysis in three different rat models of ARDS-like lung injury and local ized to pulmonary macrophages by using in situ hybridization. Also, Es cherichia coli-derived recombinant mob-1 (rmob-1) was tested for its p roperties in relationship to lung injury. Results. In vivo, intratrach eal injection of rmob-1 (50 mu g/rat) induced pulmonary leukosequestra tion (myeloperoxidase +93% +/- 8% versus control, p < 0.05) with prefe rential accumulation of neutrophils in bronchoalveolar lavage fluid (3 6.0% +/- 1.0% versus 0.1% +/- 0.1% in controls, p < 0.01). In vitro, t ranswell 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 (+1 5% +/- 0% versus rmob-1 vehicle, p < 0.01). Utilizing a rat aortic rin g 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 < 0.0 1), a major-component of the resolution phase of ARDS. Conclusions. Ta ken together, these data support the involvement of mob-1 in the patho genic mechanisms of ARDS possibly through chemotactic actions on infla mmatory cells and modulation of angiogenesis in the recovery phase of the disease.