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.
Department of Internal Medicine, Ospedale Policlinico, Milan, 20122, Italy.
F
F
Capsoni
F
F
Minonzio
C
C
Mariani
A M
AM
Ongari
P
P
Bonara
G
G
Fiorelli
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