Platelets play important roles in the late phase of the immediate hypersensitivity reaction

Background

Recent studies have shown that platelets have a role in most inflammatory reactions, but involvement of platelets in the immediate hypersensitivity reaction (IHR) in skin has not been examined.

Objective

To investigate the role of platelets in a mouse model of IgE-mediated IHR.

Methods

Mice were sensitized by injecting ovalbumin intraperitoneally and challenged by injecting ovalbumin intradermally into ears, with or without platelet depletion.

Results

Sensitized mice developed biphasic responses characterized by early-phase and late-phase reactions (LPRs). Degranulation of mast cells in skin did not differ between platelet-depleted mice and controls. The early phase reaction was not suppressed at 1 hour, but platelet depletion significantly reduced the LPR at 24 hours (P < .01). Flow cytometry showed that P-selectin expression on platelets and the number of platelet-leukocyte aggregates were both higher in the blood of ovalbumin-challenged mice compared with sham-sensitized mice at 24 hours (P < .05). In platelet-depleted mice, the LPR was restored by infusing platelets from normal mice (P < .01). This effect did not occur by infusing platelets from P-selectin–deficient mice or by pretreating platelets with anti–P-selectin antibody. Injection of activated platelet supernatant into ears led to increased leukocyte infiltration at 24 hours, and this effect was blocked by pretreating the supernatant with several antichemokine antibodies. Systemic administration of antiplatelet compounds also suppressed the LPR significantly.

Conclusion

These results show that platelets play important roles in the LPR of the IHR in skin by forming platelet-leukocyte complexes via P-selectin in blood and secreting several chemokines that attract leukocytes to skin.

Key words: Atopic dermatitis, chemokine, immediate hypersensitivity reaction, late-phase reaction, platelet, P-selectin

Abbreviations used: AD, Atopic dermatitis, APAS, Antiplatelet antiserum, CS, Control serum, IHR, Immediate hypersensitivity reaction, LPR, Late-phase reaction, MIP-1α, Macrophage inflammatory protein 1α, PAF, Platelet-activating factor, RANTES, Regulated upon activation, normal T-cell expressed and secreted, TARC, Thymus and activation-regulated chemokine, TRAP, Thrombin receptor activating peptide