CELLULAR IMMUNOLOGY 3, 86--95 (1977) Increased Spreading of Macrophages from Mice Treated with Interferon Inducers M. RABINOVITCH, R. E. MANEJIAS, M. Russo, AND E. E. ABBEY New York Universit31 Medical Center, Department of Cell Biology, 550 First Am-me, New York, New York 10016 Received A!?hgtrst 30,1976 Several interferon inducers administered iv or per OS to mice enhanced the spreading of peritoneal macrophages freshly plated on a glass surface. Spreading was scored with a microscope after the monolayers were incubated in serum-containing medium. The effective agents were a ribopolynucleotide (Poly r1: Poly rC) ,r a bacterial lipo- polysaccharide (LPS), Newcastle disease virus (NDV), tilorone, cycloheximide or pyran copolymer. However, while induction of interferon and enhanced macrophage spreading appeared to be associated, we failed to obtain significant correlation coeffr- cients between peak serum interferon titers and % of spread macrophages after the administration of NDV, tilorone or cycloheximide. Spreading was also increased by the macrophage activator C. parvztm or by intraperitoneal administration of thio- glycollate broth. Lethal preirradiation did not influence the spreading enhancement by LPS, but markedly reduced the spreading that followed the extraperitoneal adminis- tration of NDV, tilorone, cycloheximide or C. parvum, or the intraperitoneal injection of thioglycollate broth. The effect of NDV on macrophages was inhibited by prelimi- nary splenectomy. Splenectomy, however, did not influence the macrophage response to the other agents tested. The results are compatible with a direct effect of LPS on the macrophages and with an indirect, possibly lymphocyte-mediated effect of NDV. Spreading enhancement by NDV was found to be mouse-strain dependent. The re- sults provide models for the investigation of cellular or humoral mechanisms that underlie macrophage activation. INTRODUCTION Activated peritoneal macrophages rapidly spread (flatten) when plated on glass or plastic surfaces. Conditions under which this increased spreading occurs include : a) infection with microorganisms which elicit considerable cell-mediated immunity, such as Listeria or BCG 1 (1, 2) ; b) graft-versus-host reactions (3) ; c) challenge of sensitized animals with homologous antigen (4) ; d) local or sytemic adminis- tration of killed microorganisms or fractions of microorganisms such as lipopoly- saccharides (5, 6) ; or e), intraperitoneal administration of thioglycollate broth, lectins or other irritants (7, and unpublished results from this laboratory). In the first three instances macrophage activation is probably mediated by lymphokines (8). In the other instances activation may result either from direct 1 Abbreviations used in this paper : BCG, Bacillus Calmette-Guerin; LPS, lipopolysaccharide; Poly r1: Poly rC, sodium salt of polyriboinosinic: polyribocytidylic acid; NDV, New Castle disease virus ; PFU, plaque forming unit ; PMN, polymorphonuclear leukocytes ; CSF, colony stimulating factor; PBS, phosphate buffered Ca ‘+, Mg*+-free saline; N.D., not done. 86 Copyright 0 1977 by Academic I’res, Inc. All rights of reproduction in any form reserved. ISSN 0008-8749