Development of phagocytic function of cultured human monocytes is regulated by cell surface IL-10.
Monocytes differentiating in vitro into macrophages increase their capacity to ingest particles via FcgammaR and CR3. Because human recombinant IL-10 is a potent up-regulator of phagocytosis in human monocytes, we investigated whether spontaneously produced IL-10 could be a signal for the modulation of phagocytosis by cultured monocytes. We show here that culture of monocytes in the presence of anti-IL-10 mAb completely abolished up-regulation of phagocytosis of both EIgG and EIgMC3bi, suggesting a role for spontaneously produced IL-10 in the modulation of phagocytosis by cultured human monocytes. The inhibition exerted by anti-IL-10 mAb on the development of FcgammaR-mediated ingestion was dependent on the concomitant inhibition of FcgammaRIII induction in cultured cells. On the other hand, a similar down-regulation of CR3 expression was not involved in the inhibitory effect exerted by anti-IL-10 mAb on the development of CR3-mediated ingestion. Monocytes secreted detectable levels of IL-10 when cultured in medium but the concentrations of IL-10 in the supernatants decreased with length of time in culture, the decrease being completely reversed by anti-IL-10 mAb. In addition, we showed that monocytes expressed immunoreactive IL-10 on their surface and this expression increased during differentiation into macrophages. Whether this IL-10 was bound to specific membrane receptors or it was an integral membrane protein remains to be determined; however, this latter possibility is consistent with our observations that IL-10 did not elute with acid treatment and exogenous IL-10 did not increase surface staining of monocytes. Our data indicate that human mononuclear phagocytes express IL-10 on their membrane and suggest that this cytokine may represent an autocrine signal for the increased phagocytic function observed during differentiation of monocytes into macrophages.
Capsoni
F
F
Department of Internal Medicine, Ospedale Policlinico, Milan, 20122, Italy.
Minonzio
F
F
Mariani
C
C
Ongari
A M
AM
Bonara
P
P
Fiorelli
G
G
D000911:Antibodies, Monoclonal / Q000276:immunology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D010586:Phagocytes / Q000502:physiology*; D011951:Receptors, Complement / Q000096:biosynthesis; D017452:Receptors, IgG / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D011951:Receptors, Complement; D017452:Receptors, IgG; D016753:Interleukin-10