Hence, high numbers of macrophages colonize virtually all epithelial tissues early in embryogenesis, and key trophic effects of this immune cell subset have been inferred by the severely impaired growth of epithelial organs displayed by animal models deficient in macrophages or macrophage-dependent functions. Recruitment of myeloid cell populations from the bone marrow to the periphery continues to be essential in adulthood for the maintenance of tissue integrity, since, in their absence, tissue repair and regenerative events following injury are critically blunted. To date, experimental evidence indicate that macrophages may primarily influence the growth and/or regeneration of WY 14643 epithelial organs indirectly, i.e. by supporting functions such as clearance of dying cells, angiogenesis and remodeling of extracellular matrices. Whether macrophages can directly dictate select developmental options in epithelia remains presently unclear. During pancreatic development, at E14.5–15.5 gestational age, epithelial progenitors emerge from a rudimentary ductal tree through a regulated sequence of events that includes withdrawal from the cell cycle, delamination into the surrounding mesenchyme and differentiation into endocrine or exocrine cell types. As such, while providing a pool of progenitors competent to execute specific developmental steps and make divergent lineage choices, the E14.5/E15.5 pancreas represents a valuable model to study how such epithelial programs might be impacted on by other exogenous cellular cues. In this regard, in vivo and in vitro studies have provided evidence that,WZ4002 over-imposed to a hierarchy of transcription factors expressed by the epithelium, interactions of the epithelium with the pancreatic mesenchyme govern the balance between the exocrine and the endocrine developmental fate of progenitors and are required for the growth of the pancreatic epithelial compartment as a whole. At present, few studies have reported the presence of tissue macrophages within the pancreatic mesenchyme and noted reduced growth of endocrine cells in their absence. However, the possible role of macrophages as regulators of select developmental events in the pancreatic epithelium remains unknown. A corollary to this question is whether diverse states of activation of tissue macrophages differentially affect pancreatic developmental programs. Indeed, macrophages resident within tissues may adopt a spectrum of functional states. At the extreme of this spectrum are classically and alternatively activated macrophages. M1 phenotypes are acquired by macrophages upon encounter with pathogens, and lead to the production of high levels of pro-inflammatory mediators and reactive nitrogen intermediates that contribute to pathogen clearance. Conversely, ‘‘alternative’’ or M2 activation states are characterized by the production of lower levels of pro-inflammatory cytokines, synthesis of decoy anti-inflammatory receptors, little or no nitrogen derivatives, as well as production of mediators of tissue remodeling. As such, M2 macrophages have immuneregulatory functions that dampen inflammation and promote repair during wound healing.