Interleukin 8 and mast cell-generated tumor necrosis factor-alpha in neutrophil recruitment.
In the reverse passive Arthus reaction in mouse skin and immune injury of mouse dermal basement membrane, neutrophil (PMN) infiltration in mast cell deficient WBB6F1-W/Wv (W/Wv) mice was only 40% of that in WBB6F1-(+)/+ (+/+) mice that had a normal mast cell repertoire. An anti-tumor necrosis factor-alpha (TNF-alpha) monoclonal antibody (mAb) decreased PMN infiltration by 35-80% in +/+ but not W/Wv mice. In addition, an anti-human interleukin-8 (IL-8) MAb, DM/C7, inhibited PMN infiltration of the skin induced by either intradermal administration of recombinant human IL-1 beta or immune complex deposition. In both models of immune complex injury, DM/C7 reduced PMN infiltration by 40-60% in +/+ mice but not W/Wv mice. PMN infiltration and the sensitivity of this infiltration to anti-TNF-alpha or DM/C7 MAb in W/Wv mice whose mast cell population had been restored was indistinguishable from the influx observed in +/+ mice. These data suggest that TNF-alpha, IL-8, and mast cells play a fundamental role in PMN recruitment following immune complex injury.
Zhang
Y
Y
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110.
Ramos
B F
BF
Jakschik
B
B
Baganoff
M P
MP
Deppeler
C L
CL
Meyer
D M
DM
Widomski
D L
DL
Fretland
D J
DJ
Bolanowski
M A
MA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000276:immunology; D001183:Arthus Reaction; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D007375:Interleukin-1 / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology / Q000494:pharmacology*; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology*; D011994:Recombinant Proteins; D012867:Skin / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D007375:Interleukin-1; D016209:Interleukin-8; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha