Priming of eosinophil recruitment in vivo by LPS pretreatment.
Eosinophils are important inflammatory cells in allergic diseases. Recent evidence suggests that priming mechanisms in the blood may be important for effective eosinophil recruitment to sites of allergic inflammation. We have investigated whether priming an inflammatory site could enhance eosinophil recruitment in vivo. Pretreatment of skin sites in the guinea pig with a low dose (30 ng) of LPS, which had little effect on eosinophil accumulation alone, enhanced by up to threefold the 111In-eosinophil accumulation in response to a passive cutaneous anaphylactic reaction and to intradermally injected eosinophil chemoattractants (leukotriene B4, PAF, and C5ades Arg). In contrast, LPS pretreatment did not enhance accumulation of 111In-neutrophils. Priming was seen only with a 1-h pretreatment time and was not associated with an increase in local edema or a change in cutaneous blood flow. It was independent of local protein synthesis, as assessed using cycloheximide, and was unaffected by a PAF antagonist, a 5-lipoxygenase inhibitor, and the IL-1 receptor antagonist. The priming response was, however, reduced by co-injection with the LPS of TNFR-IgG, but not of CD4-IgG. Blockade of CD18 showed this adhesion molecule to be critical for eosinophil accumulation, and LPS-primed sites were inhibited as effectively as nonprimed sites. In conclusion, low dose LPS pretreatment of guinea pig skin sites primes for eosinophil accumulation induced by intradermally injected inflammatory mediators and cutaneous anaphylactic reaction. This may be an important process by which eosinophil recruitment is modulated in vivo.
Macari
D M
DM
Department of Applied Pharmacology, Imperial College of Science, Technology & Medicine, London, United Kingdom.
Teixeira
M M
MM
Hellewell
P G
PG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics; D001381:Azepines / Q000494:pharmacology; D018821:CD18 Antigens / Q000276:immunology; D002631:Chemotactic Factors, Eosinophil / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D015937:Complement C5a, des-Arginine / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004357:Drug Synergism; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D004802:Eosinophilia / Q000139:chemically induced* / Q000503:physiopathology; D004804:Eosinophils / Q000187:drug effects*; D005260:Female; D006168:Guinea Pigs; D007074:Immunoglobulin G / Q000494:pharmacology; D053590:Interleukin 1 Receptor Antagonist Protein; D007958:Leukocyte Count / Q000187:drug effects; D007975:Leukotriene B4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010323:Passive Cutaneous Anaphylaxis; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011714:Pyrans / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D014230:Triazoles / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001381:Azepines; D018821:CD18 Antigens; D002631:Chemotactic Factors, Eosinophil; D015937:Complement C5a, des-Arginine; D007074:Immunoglobulin G; D053590:Interleukin 1 Receptor Antagonist Protein; D008070:Lipopolysaccharides; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; D011500:Protein Synthesis Inhibitors; D011714:Pyrans; D015363:Quinolones; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011993:Recombinant Fusion Proteins; D012795:Sialoglycoproteins; D014230:Triazoles; C052518:WEB 2086; C088450:ZM 230487; D007975:Leukotriene B4; D015054:Zymosan; D003513:Cycloheximide