MEDIATION OF LUNG NEUTROPHIL UPTAKE AFTER ENDOTOXIN BY CD18-INTEGRIN-DEPENDENT AND CD18-INTEGRIN-INDEPENDENT MECHANISMS

We studied polymorphonuclear neutrophil (PMN) uptake in lungs of endot oxemic rabbits using In-111-labeled PMN and isotope imaging by gamma s cintigraphy. Rabbits were challenged intravenously with 100 mu g Esche richia coli endotoxin either 4 or 24 h before an intravenous injection of In-111-labeled PMN, which was obtained from donor rabbits. The con tribution of CD18 glycoprotein (beta(2)-integrin) on PMN was examined using an anti-CD18 monoclonal antibody (MAb) IB4 infused 20 min before In-111-labeled PMN injection. In control rabbits, In-111-labeled PMN uptake in lungs was maximal within 5 min [136 +/- 2% increase above ba seline (+/-SE)] and then fell exponentially with a disappearance half- time (t1/2) of 10 +/- 2 min. In rabbits challenged with endotoxin for either 4 or 24 h, maximum In-111-labeled PMN lung uptake and t1/2 valu es increased to 52 +/- 3 and 56 +/- 3% and to 26 +/- 2 and 31 +/- 6 mi n, respectively. Pretreatment with MAb IB4 (0.5 mg/kg iv) did not alte r the PMN uptake response and t1/2 values in the 4-h endotoxin-challen ged rabbits (i.e., maximum uptake of 52 +/- 3% above baseline and t1/2 of 26 c 2 min), whereas MAb IB4 prevented the increases in lung PMN u ptake and t1/2 in 24-h endotoxin-challenged rabbits (maximum PMN uptak e of 26 +/- 5% and t1/2 of 7 +/- 3 min; P < 0.001). In contrast, the c ontrol MAb OKM-1 did not prevent lung PMN uptake and the disappearance of PMN from lungs at either times. These results indicate that endoto xemia stimulates an early CD18-independent PMN uptake in lungs and a l ate PMN uptake response mediated by CD18 integrin-dependent mechanisms .