| First Author | Todt JC | Year | 2008 |
| Journal | J Leukoc Biol | Volume | 84 |
| Issue | 2 | Pages | 510-8 |
| PubMed ID | 18511575 | Mgi Jnum | J:138416 |
| Mgi Id | MGI:3805138 | Doi | 10.1189/jlb.0307135 |
| Citation | Todt JC, et al. (2008) The scavenger receptor SR-A I/II (CD204) signals via the receptor tyrosine kinase Mertk during apoptotic cell uptake by murine macrophages. J Leukoc Biol 84(2):510-8 |
| abstractText | Apoptotic cells (AC) must be cleared by macrophages (Mo) to resolve inflammation effectively. Mertk and scavenger receptor A (SR-A) are two of many receptors involved in AC clearance. As SR-A lacks enzymatic activity or evident intracellular signaling motifs, yet seems to signal in some cell types, we hypothesized that SR-A signals via Mer receptor tyrosine kinase (Mertk), which contains a multisubstrate docking site. We induced apoptosis in murine thymocytes by dexamethasone and used Western blotting and immunoprecipitation to analyze the interaction of Mertk and SR-A in the J774A.1 (J774) murine Mo cell line and in peritoneal Mo of wild-type mice and SR-A-/- mice. Phagocytosis (but not adhesion) of AC by J774 was inhibited by anti-SR-A or function-blocking SR-A ligands. In resting J774, SR-A was associated minimally with unphosphorylated (monomeric) Mertk; exposure to AC induced a time-dependent increase in association of SR-A with Mertk in a direct or indirect manner. Anti-SR-A inhibited AC-induced phosphorylation of Mertk and of phospholipase Cgamma2, essential steps in AC ingestion. Relative to tissue Mo of wild-type mice, AC-induced Mertk phosphorylation was reduced and delayed in tissue Mo of SR-A-/- mice, as was in vitro AC ingestion at early time-points. Thus, during AC uptake by murine Mo, SR-A is essential for optimal phosphorylation of Mertk and subsequent signaling required for AC ingestion. These data support the Mertk/SR-A complex as a potential target to manipulate AC clearance and hence, resolution of inflammation and infections. |
