Endotoxin (LPS) stimulates in vitro migration of macrophages from LPS-resistant mice but not from LPS-sensitive mice.

Abstract

LPS induces strikingly different inflammatory responses in LPS-resistant and -susceptible mice. The present study was made to investigate the effects of LPS on the in vitro migration of macrophages and polymorphonuclear leukocytes from such animals. LPS, in the absence of serum, stimulated the chemokinetic migration of elicited macrophages from the LPS-resistant C3H/HeJ and C57BL10/ScCR mice, whereas migration of macrophages from the susceptible C3H/HeN and C57BL10/SN mice was either unaffected or slightly depressed by LPS. Doses of LPS as low as 50 ng/ml induced chemokinesis of C3H/HeJ macrophages. The strain differences between resistant and susceptible mice were observed with several different LPS preparations. In contrast, macrophage Chemotaxis towards zymosan- or LPS-activated mouse serum was similar in resistant and susceptible strains. Deproteinized LPS and lipid A preparations also induced migration of C3H/HeJ macrophages, whereas treatment of LPS with polymyxin B abolished its stimulatory effects. Macrophages from C3H/HeJ mice must therefore respond to the lipid A moiety of LPS. We found no evidence that the strain characteristic migratory responses to LPS were influenced by differential stimulation of arachidonic acid metabolism by LPS in the cells: indomethacin, an inhibitor of prostaglandin synthesis, did not alter migration to either LPS- or zymosan-activated mouse serum in macrophages from resistant or susceptible mice; in contrast, NDGA and ETYA, inhibitors of the production of potentially chemotactic HETE, reduced migration toward both LPS- and zymosan-activated mouse serum by C3H/HeJ macrophages and toward zymosan-activated mouse serum by C3H/HeN macrophages. Strain differences in migratory responses to LPS were restricted to macrophages in that polymorphonuclear leukocytes of both strains failed to respond to LPS. Interestingly, these in vitro findings correlate with some of the in vivo inflammatory responses to LPS in resistant and susceptible mice.