Resolution-phase macrophages possess reduced bactericidal properties compared with M1 cells. (A) Macrophages (0.5 × 106) were isolated from a 72-hour peritonitis that either resolved (0.1 mg zymosan or rM macrophages, □) or progressed to systemic inflammation (10 mg zymosan or M1 macrophages, ■) and incubated with S aureus. One hour later, media were taken and plated on LB-agar plates and bacterial colonies counted 24 hours later as a measure of macrophage ability to kill bacteria. Thus, the higher CFU reflect reduced bacterial clearance. In the first instance, macrophages from resolving inflammation (rM) had a lower ability to kill S aureus compared with M1 cells. However, upon incubation with the cAMP inhibitor, rp-cAMP, rM cells experienced enhanced bactericidal properties. Conversely, M1 cells, whose inherent ability to kill bacterial was greater than that of rM cells, were reduced by elevating cAMP. (B) Theophylline was injected to animals bearing an ongoing inflammation (10 mg zymosan) at 72 hours followed by group B streptococcus with plasma sampled 3 hours later to determine colony-forming units along with (C) animal survival over time at concentrations of drug that (D) elevated cAMP. n = 8 mice per group. *P ≤ .05; **P ≤ .01; and ***P ≤ .001, as determined by ANOVA, followed by Bonferroni t test with data expressed as mean plus or minus SEM.
