NEUTROPENIC RESPONSES TO INTRADERMAL INJECTIONS OF ESCHERICHIA-COLI - EFFECTS ON THE KINETICS OF POLYMORPHONUCLEAR LEUKOCYTE EMIGRATION

Abstract

Killed Escherichia coli organisms injected intradermally into rabbits induced significant neutropenia and provoked a rapid rise in body temperature. Both the magnitude and the duration of the neutropenia were dose-dependent. After recovery from neutropenia, the rabbits became refractory to its redevelopment when subsequently given an equivalent dose of E. coli. The influence of neutropenia and the subsequent refractory period on the rate of polymorphonuclear leukocyte (PMN) emigration into inflammatory sites was examined. Killed E. coli organisms (6 .times. 108 per site) were injected into two groups of 20 intradermal sites in each rabbit. The first group (Group F) preceded the second (Group S) by 6 hours. The kinetics of PMN emigration, quantitated with 51Cr-labeled cells, differed in the two groups. In Group S sites an intense PMN influx was measured at 0-4 hours, and subsequently the extent of PMN emigration rapidly declined. In Group F sites a minute PMN influx was detected during the first 4 hours, coinciding with a marked neutropenia. The maximal PMN influx into Group F sites was measured between 6 and 10 hours. Microscopic sections at 4 hours showed a scanty PMN infiltrate and numerous bacteria in the dermis of Group F sites, while extensive phagocytosis of bacteria by PMNs was apparent in Group S sites. By comparing the extent of bacterial phagocytosis in 4-hour-old sites with the magnitudes of PMN emigration between 6 and 10 hours in both groups, we concluded that the phagocytic elimination of killed E. coli was not a major mechanism regulating the cessation of local PMN emigration. Instead, we propoose that tachyphylaxis or desensitization of sites to inflammatory factors released from E. coli is the responsible mechanism.