Absence of requirement for polymorphonuclear granulocytes in the acute antibody-mediated rejection of murine skin allografts.

Abstract

The role of polymorphonuclear granulocytes (PMN) in acute antibody-mediated rejection (AAR) was studied in a murine skin allograft model. B10.A skin was grafted onto B10.D2 recipients that were treated with goat antimouse lymphocyte serum, to postpone cellular rejection. This prolonged the median survival time of the grafts to 21.5 +/- 1.0 days. PMN depletion was effected by total body irradiation of 6.0 Gy (600 rads) on day 4 after grafting, which reduced the number of PMN in the circulation to levels below 150/microliters from days 3-10 after the irradiation. To induce AAR the mice received, on day 8 after grafting, an i.v. injection of a monoclonal antibody with specificity against the donor H-2Kk antigen together with 0.25 ml fresh rabbit serum. This caused acute rejection of all grafts in the control group within 72 hr, with abundant presence of PMN in the graft vessels on histologic examination. In PMN-depleted recipients the reaction in the grafts was somewhat retarded in th first 24 hr, but nevertheless acute rejection occurred within 72 hr in 9 of 11 animals, whereas PMN were virtually absent from the grafts. The results show that PMN act as accelerators and amplifiers of the acute antibody-mediated rejection process, but are not essential mediators in the damage to the vascular endothelium of the grafts.