Transcriptional profile of WT and Mmp10-/- bone marrow-derived macrophages after infection with Pseudomonas aeruginosa

ABSTRACT: Several members of the matrix metalloproteinase (MMP) family control specific immune processes, such as leukocyte influx and chemokine activity. Stromelysin-2 (MMP10) is expressed in numerous tissues after injury; however, little is known of its function. Here, we report that MMP10 is expressed by macrophages in human lungs from patients with cystic fibrosis and induced in mouse macrophages in response to Pseudomonas aeruginosa infection both in vivo and in cultured bone marrow-derived macrophages (BMDM). Whereas all wildtype mice were alive at 48 h post-infection, all Mmp10–/– mice had greater weight loss and died or reached euthanasia criteria with no defect in bacterial clearance. Rather, macrophage numbers in infected Mmp10–/– lungs were about 3-4-fold greater than in wildtypes. Demonstrating that the protective effect of MMP10 was due its production by macrophages, adoptive transfer of wildtype BMDM normalized infection-induced weight loss in Mmp10–/– recipients to wildtype levels. In vivo, the expression of several M1 macrophage markers were elevated and M2 markers reduced in Mmp10–/– lungs, and we saw similar differences between M1-activated wildtype and Mmp10–/– BMDM. Global gene expression analysis revealed that infection-mediated transcriptional changes persisted in Mmp10–/– BMDM long after they downregulated in wildtype cells. These results indicate that MMP10 serves a beneficial role in response to infection by moderating the pro-inflammatory response of infiltrating macrophages. Total RNA from bone marrow-derived macrophages from 3 WT and 3 Mmp10-/- mice for each treatment: media change only, 6h post PA infection or 24 h post PA infection. Samples were hybidized to 18 Affymetrix GeneChip Mouse Gene 2.0 ST arrays.

ORGANISM(S): Mus musculus

SUBMITTER: Ryan McMahan 

PROVIDER: E-GEOD-78175 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress