Abstract
The role of macrophage-like cells in natural resistance of mice to transplants of foreign bone marrow cells was reinvestigated by means of the fractionated forms of carrageenan designated as ι, λ, and κ, and the unfractionated form Seakem-9 for comparison. All these anti-macrophage agents weakened resistance to parental and allogeneic marrow grafts when a single small dose (0.5 mg/mouse) was injected i.v. into irradiated mice several hours before or after transplantation. λ and ι carrageenans were more effective than the SK and κ forms, and the anti-resistance effect was enhanced when irradiation preceded transplantation by 20 to 24 hr. κ and λ carrageenans had no adverse effect on the homing of donor stem cells to the spleen and on subsequent proliferation. Stem cells recovered from the spleens of genetically resistant mice given ι-carrageenan were of donor type, as determined by retransplantation into discriminant hosts. The combined effect of suboptimal doses of λ-carrageenan and rabbit anti-mouse lymphocyte serum was additive. Since the antiserum was a blocking agent for accessory macrophage-like cells interacting with effector lymphocytes, this result suggested that λ-carrageenan injured macrophages. Accordingly, agents sharing with carrageenans the anti-complementary, anti-coagulant, or Hageman factor-activating properties, but not toxicity for macrophages, failed to weaken resistance, and mice with genetic defects of complement components were as resistant and as sensitive to the effect of carrageenans as normal mice. These experiments reiterate the importance of anti-macrophage agents in weakening natural resistance to hemopoietic cells and in elucidating cellular mechanisms.