Mediation of lung neutrophil uptake after endotoxin by CD18-integrin-dependent and -independent mechanisms.
We studied polymorphonuclear neutrophil (PMN) uptake in lungs of endotoxemic rabbits using 111In-labeled PMN and isotope imaging by gamma scintigraphy. Rabbits were challenged intravenously with 100 micrograms Escherichia coli endotoxin either 4 or 24 h before an intravenous injection of 111In-labeled PMN, which was obtained from donor rabbits. The contribution of CD18 glycoprotein (beta 2-integrin) on PMN was examined using an anti-CD18 monoclonal antibody (MAb) IB4 infused 20 min before 111In-labeled PMN injection. In control rabbits, 111In-labeled PMN uptake in lungs was maximal within 5 min [36 +/- 2% increase above baseline (+/- 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 111In-labeled PMN lung uptake and t1/2 values increased to 52 +/- 3 and 56 +/- 3% and to 26 +/- 2 and 31 +/- 6 min, respectively. Pretreatment with MAb IB4 (0.5 mg/kg iv) did not alter the PMN uptake response and t1/2 values in the 4-h endotoxin-challenged rabbits (i.e., maximum uptake of 52 +/- 3% above baseline and t1/2 of 26 +/- 2 min), whereas MAb IB4 prevented the increases in lung PMN uptake and t1/2 in 24-h endotoxin-challenged rabbits (maximum PMN uptake of 26 +/- 5% and t1/2 of 7 +/- 3 min; P < 0.001). In contrast, the control MAb OKM-1 did not prevent lung PMN uptake and the disappearance of PMN from lungs at either times.(ABSTRACT TRUNCATED AT 250 WORDS)
McCandless
B K
BK
Department of Physiology and Cell Biology, Albany Medical College, New York 12208.
Kaufman
R P
RP
Cooper
J A
JA
Neumann
P H
PH
Malik
A B
AB
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000494:pharmacology*; D018821:CD18 Antigens; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D005720:Gamma Rays; D007275:Injections, Intravenous; D016023:Integrins / Q000502:physiology*; D008099:Liver / Q000166:cytology; D008168:Lung / Q000166:cytology* / Q000000981:diagnostic imaging / Q000187:drug effects; D009504:Neutrophils / Q000502:physiology*; D011817:Rabbits; D011859:Radiography; D013154:Spleen / Q000166:cytology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D004731:Endotoxins; D016023:Integrins