title: Recruitment of neutrophils during IgE-dependent cutaneous late phase reactions in the mouse is mast cell-dependent. Partial inhibition of the reaction with antiserum against tumor necrosis factor-alpha.
abstract: Much of the clinically important pathology associated with IgE-dependent disorders is thought to reflect the actions of the blood-borne leukocytes recruited during these responses. To evaluate the extent to which mast cells are responsible for the leukocyte infiltration associated with IgE-dependent cutaneous reactions, we attempted to elicit these responses in normal mice, genetically mast cell-deficient W/Wv mice, and in W/Wv mice selectively repaired of their mast cell deficiency by the intradermal injection of cultured mast cells derived from the congenic normal (+/+) mice. We found that the tissue swelling associated with IgE-dependent passive cutaneous anaphylaxis reactions developed rapidly and diminished markedly from 2 to 4 h after antigen challenge, but remained detectable for at least 24 h after elicitation of the responses. Infiltration of leukocytes (predominantly neutrophils) also occurred at these sites, but reached maximal levels 6-12 h after antigen challenge, persisted at high levels for 24 h, and largely waned by 48 h. Virtually all of the tissue swelling and leukocyte infiltration associated with IgE-dependent cutaneous reactions was mast cell dependent. Intradermal injection of 40 U of recombinant murine TNF-alpha (rmTNF-alpha) elicited neutrophil infiltration similar in magnitude and kinetics to that observed after IgE-dependent mast cell degranulation. A rabbit anti-rmTNF-alpha (R anti-rmTNF-alpha) antiserum, which was able to inhibit 84% of the neutrophil infiltration observed after i.d. injection of rmTNF-alpha, inhibited IgE-, and mast cell-dependent leukocyte infiltration by 47 +/- 7% in three separate experiments. These findings indicate that TNF-alpha contributes to mast cell-dependent recruitment of leukocytes during IgE-dependent cutaneous late phase reactions, but suggest that other mast cell-associated mediators probably also contribute to this response.
authors.affiliation: Department of Pathology, Beth Israel Hospital, Boston, Massachusetts 02215.
authors.forename: B K
authors.initials: BK
authors.lastname: Wershil
authors.forename: Z S
authors.initials: ZS
authors.lastname: Wang
authors.forename: J R
authors.initials: JR
authors.lastname: Gordon
authors.forename: S J
authors.initials: SJ
authors.lastname: Galli
mesh_terms: D000818:Animals; D003872:Dermatitis / Q000378:metabolism / Q000503:physiopathology*; D007106:Immune Sera; D007073:Immunoglobulin E / Q000378:metabolism*; D007962:Leukocytes / Q000502:physiology; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D009504:Neutrophils / Q000502:physiology*; D012867:Skin / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D007106:Immune Sera; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E