Neutrophil recruitment as a factor limiting injury or promoting recovery from acute lung injury

We studied 1) neutrophil mobilization in sheep given endotoxin (10 ng . kg(-1). min(-1), n = 5) for 4 h, 2) surviving (n = 17) and nonsurviving sheep (n = 8) during a 12-h infusion of endotoxin, and 3) adult sheep (n = 8) or lambs (n = 8) infused with endotoxin for 12 h. Bone marrow cells of sheep declined from a baseline value of 10,533 +/- 1,784 to 5,966 +/- 1,980 cells/mu l (P < 0.05) 4 h after endotoxin. After 12 h of endotoxin infusion, circulating neutrophils remained reduced from baseline values of 2,000-4,000 cells/mu l to 343 +/- 70 in lambs and 484 +/- 236 in nonsurviving sheep, while beginning to recover in surviving sheep to 1,838 +/- 467 cells/mu l. In lambs and nonsurviving sheep, a 12-h infusion of endotoxin increased lung lymph protein clearance tenfold compared with a five-fold increase in surviving sheep. Neutrophils cultured from sheep bone marrow exposed to lamb postendotoxin plasma failed to increase in cell number (609 +/- 229 to 610 +/- 182 cells/mu l), whereas similar cells exposed to adult sheep postendotoxic plasma showed a significant increase in cell number (1,069 +/- 101 to 2,293 +/- 448 cells/mu l, P < 0.05). Our results are consistent with the hypothesis that the ability to recruit neutrophils to the circulation during periods of inflammation is important in limiting the severity of acute lung injury.