Background/Purpose: Diffusealveolar hemorrhage (DAH) is an infrequent but life-threatening complication in patients with systemic lupus erythematosus (SLE). Cells of the monocyte/macrophage lineage are essential to the pathogenesis of lung hemorrhage.An increasing number of research proved that Axl receptor tyrosine kinase(AxlTK)was especially highly expressed in macrophages. In this study, we explore whether AxlTK affects pathogenesis in DAH mice model by regulating macrophage polarization.

Methods: Bone marrow cells were obtained from femurs and tibias of Axl KO and WT Mice. Bone marrow-derived macrophages (BMDMs) were stimulated with 50ng/ml LPS and 20 ng/ml IFN-γ to promote M1 polarization, or 50ng/ml IL-4 to induce M2 polarization, respectively. Then, macrophages were examined by flow cytometry (FCM). At 8-10 weeks of age, wild type (WT) and Axl KO mice received a single intraperitoneal injection of 1 ml of pristane. After 14 daysof incubation, lung tissues were harvested and stained with H&E. And single-cell suspensions from lungs tissues were stained with the corresponding Ab mixtures for marking M1 and M2 macrophages. Cells were analyzed using a flow cytometry system.

Results: The expression of iNOS(M1 marker)and CD206(M2 marker) on BMDMs were significantly decreased in Axl KO compared to WT mice, respectivety. Significantly, lungs tissues from Axl KO mice with no or partial or complete hemorrhage, whereas those from WT mice showedpartial or complete hemorrhage in pristane-induced DAH micemodel. Mechanically, the expression of iNOS on macrophges in lungs tissues of Axl KO mice also showed a significantly decreased, while the expression of CD206 were slightly increased as compared to WT mice.

Conclusion: AxlTK may promotes macrophage polarization towards M1 and M2and ameliorates pristane induced diffuse alveolar hemorrhage in mice.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/axl-receptor-tyrosine-kinase-ameliorates-pristane-induced-diffuse-alveolar-hemorrhage-in-mice-by-regulating-macrophage-polarization/