The novel chemokine mob-1: involvement in adult respiratory distress syndrome.
BACKGROUND
Using differential display reverse transcriptase-polymerase chain reaction we have recently identified mob-1, the novel rat homologue of the human alpha-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 up-regulation 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 micrograms/rat) induced pulmonary leukosequestration (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). In 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 chemotaclic actions on inflammatory cells and modulation of angiogenesis in the recovery phase of the disease.
Abdullah
F
F
Department of Surgery, Jefferson Medical College, Philadelphia, PA 19107-5083, USA.
Ovadia
P
P
Feuerstein
G
G
Neville
L F
LF
Morrison
R
R
Mathiak
G
G
Whiteford
M
M
Rabinovici
R
R
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D054357:Chemokine CXCL10; D018925:Chemokines / Q000096:biosynthesis*; D019743:Chemokines, CXC; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology; D003001:Cloning, Molecular; D016207:Cytokines / Q000096:biosynthesis* / Q000633:toxicity; D017931:DNA Primers; D004195:Disease Models, Animal; D004926:Escherichia coli; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000633:toxicity; D012128:Respiratory Distress Syndrome / Q000276:immunology* / Q000473:pathology; D014158:Transcription, Genetic
C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; C091326:Cxcl10 protein, rat; D016207:Cytokines; D017931:DNA Primers; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2