Figure 1.

Roles of inflammatory macrophages in acinar cell metaplasia and formation of ADM lesions. Acinar cells with oncogenic Kras mutations upregulate expression of ICAM1, which as a shedded, soluble form (sICAM1) can attract inflammatory M1 macrophages (IM). These most likely originate from tissue resident populations. IM M1 once present at acini produce factors that inhibit alternatively-activated M2 macrophages (AAM), but also factors that drive acinar cell metaplasia to a duct-like phenotype. This acinar-to ductal metaplasia or ADM is driven by the IM secreted cytokines/chemokines TNF, CCL5, IL-6, and IL-1α, or by MMPs. Resulting ADM lesions are the earliest lesions that have been implicated in inducing the formation of pancreatic cancer. ADM can secrete molecules such as CCL2 and CCL10, which have been implicated in further recruitment of macrophages and monocytes. Created with BioRender.com.