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The biologic activity of mast cell granules in rat skin: effects of adrenocorticosteroids on late-phase inflammatory responses induced by mast cell granules

Journal of Allergy and Clinical Immunology
Publication Date
DOI: 10.1016/0091-6749(81)90190-1
  • Medicine


Abstract Mast cell degranulation in rat skin in response to Compound 48 80 , anti-IgE or to the intradermal injection of purified rat peritoneal mast cell granules (MCG) produces a late-phase response (LPR) characterized by polymorphonuclear infiltrates at 2 to 8 hr followed by mononuclear cell infiltrates at 24 to 48 hr. MCG generate LPR in a dose-related fashion; 1 μg is sufficient to produce discernible LPR, whereas 5 μg attract ≥ 150 cells/high-powered field (3+ to 4+ response) in rat skin after 8 and 24 hr. Infiltrates producing 3+ responses are also induced by 5 μg of two partially purified factors obtained from solubilized MCG by ultrafiltration: a high molecular weight (HMW) fraction containing molecules >10,000 daltons and a low molecular weight (LMW) fraction with a molecular weight of 500 to 10,000. The effect of depletion of endogenous corticosteroids on LPR was studied in adrenalectomized, sham-operated, and nonoperated littermates. LPRs were induced by 5 μg each of MCG, HMW and LMW fractions, and anti-IgE. Adrenalectomized, sham-operated, and normal nonoperated littermates expressed equivalent LPRs. Thus adrenalectomy has no detectable effect on LPR after mast cell degranulation. The dose-response effects of exogenous corticosteroids on LPR were assessed by pretreating rats with hydrocortisone, methylprednisolone, or dexamethasone. Normal rats injected with methylprednisolone (0.5 to 500 μg), hydrocortisone (0.4 to 400 μg), or dexamethasone (7.6 μg) per 24 hr for 3 days had significantly suppressed LPRs after 8 or 24 hr in response to anti-IgE, MCG, HMW, or LMW fractions. Within 1 day of hydrocortisone (400 μg) pretreatment, the LPR induced by anti-IgE and MCG were considerably reduced. Thus there are at least two separate constituents of MCG capable of eliciting late-phase inflammatory responses in rat skin, and corticosteroids may prevent the LPR thereby elicited. The capacity of corticosteroids to suppress LPR may contribute to their clinical usefulness in treating allergic diseases.

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