Recombinant human gamma-interferon induces human monocyte polykaryon formation.

Abstract

Monocyte or macrophage polykaryons (MP) are seen in different tissues in various inflammatory states and in normal bone (osteoclasts). The factors controlling the formation and the function of MP are not completely understood. The effects of the lymphokine .gamma.-interferon (IFN-.gamma.) on human monocyte function was evaluated in vitro. Purified recombinant IFN-.gamma. [20-200 U/ml (0.1-1.0 nM)] caused the appearance of MP in cultures of normal human monocytes cultured in 10% unheated autologus serum. The MP were noted by as early as 36 h of culture with fusion indices of 40-60% and up to 160 nuclei/cell. The effect was seen with both recombinnat IFN-.gamma. and natural IFN-.gamma. produced by Staphylococcal enterotoxin A-stimulated lymphocytes, but IFN-.alpha. (leukocyte-derived and recombinant) and IFN-.beta. did not induce MP formation. The activity of the IFN-.gamma. was destroyed by heating at 56.degree. C for 4 h, incubating at pH 2 for 3 h, or incubating with antibody against IFN-.gamma.. Populations of monocytes incubated 3 days with 100 U of IFN-.gamma./ml (0.5 nM) had enhanced capacity to produce H2O2 in response to phorbol 12-myristate 13-acetate and increased content of acid phosphatase and plasminogen activator. As determined by autoradiography, the MP did not incorporate [3H]dThd into their nuclei. The IFN-.gamma. appears to induce MP formation by a process of monocyte fusion, and to activate monocytes, as judged by various parameters.