Stimulation of adenosine receptors on myeloid cells enhance leukocyte migration at the site of burn injury

Abstract

Adenosine, endogenous purine nucleoside, is an ATP metabolite that also acts as an extracellular signaling molecule. The concentration of extracellular adenosine rises during hypoxia and cell damage leading to numerous pleiotropic effects. Although a high concentration of adenosine was found at burn injury, the effect has not been well elucidated. We have studied human peripheral blood myeloid cell, due to their expression of specific adenosine receptors and capacity to migrate to the site of burn injury. We have shown that myeloid cells after 72 hours of stimulation of adenosine receptors develop altered expression of surface antigens: preserved monocyte's marker CD14 with already expressed dendritic cell markers (CD209, CD1a). Whereas untreated cells have already lost monocyte marker in 72 hours, and express CD1a more abundantly. Adenosine modified myeloid cells express also higher levels of mRNA of proinflammatory cytokines and chemoattractants (IL-6, IL-8, IL-1 b). Using mouse model of the burn injury we have shown, that adenosine modified bone marrow derived myeloid cells injected in the site of the injury promote migration of granulocytes, monocytes, macrophages, and fibroblasts on the 7th day after burn. Thus, stimulation of adenosine receptors alters differentiation and function of myeloid cells. In the site of burn injury adenosine modified myeloid cells augment cell migration due to paracrine factors.